Difference Between Acetaminophen And Ibuprofen – Which One Should You Take?

Difference between acetaminophen and ibuprofen – which one is better for you? Who isn’t familiar with NSAIDs, the most common pain-killers and our number one go-to medicines when we are suffering from a headache or fever.

Aleve, Ecotrin and Advil are some of the names that are on the tip of everybody’s tongue. And because of the common availability and extreme popularity of these drugs, many of us often wonder what is the difference between them, if any.

Of all the pain killers, the biggest debate is seen between Acetaminophen (Tylenol) and ibuprofen (Advil) – the two most frequently employed analgesics, both in adults and in pediatrics in the US, Europe and globally.

Difference Between Acetaminophen And Ibuprofen

The most common question many ask is whether they should prefer acetaminophen over ibuprofen when they have fever, pain or swelling and vice versa. They often wonder which of the two would give best and fastest result.

Here is where you will get the most reliable answer to your most nagging questions.

For starters, Tylenol (chemical name: paracetamol or acetaminophen) is not an NSAID. An NSAID, an acronym for non-steroidal anti-inflammatory drug, is a drug that exhibits anti-inflammatory effect as its chief property. Acetaminophen lacks anti-inflammatory action which brings it outside the group.

Drugs that qualify as NSAIDs are aspirin (Ecotrin, Bufferin), naproxen (Aleve, Naprelan), meclofenamic acid (Ponstan), sulindac (Clinoril) and ibuprofen (Advil).

Despite not belonging to the particular class of drugs, acetaminophen is closely related to NSAIDs since it exhibits the exact same function save the anti-inflammatory effect.

So, what we have learned so far is that acetaminophen is not the ideal drug if you have inflammation, swelling, muscle sprain or arthritis. It is best used for fever and pain. Let us now compare both drugs for their mechanism of action, indications and adverse effects so that you will get a clearer picture.

Difference Between Acetaminophen And Ibuprofen: Mechanism of Action

Ibuprofen: The exact mechanism of action of ibuprofen is unknown. It is thought to act non-selectively on cyclooxygenase (COX) enzyme that is responsible for the conversion of arachidonic acid into prostaglandins – the chief inflammatory mediators that kick-start an inflammatory process in the body and lower pain threshold in the brain. In simple words, prostaglandins sensitize your body to pain and inflammation and ibuprofen stops the cycle before it starts.

Acetaminophen: has more or less similar action as ibuprofen but it acts chiefly on COX-2 enzyme. When COX-2 is inhibited, arachidonic acid is not metabolized to prostaglandins H2 and E2. Prostaglandin E2 (PE2) lowers hypothalamic-set point in the brain and increases body temperature.

Your body’s thermoregulatory system is located in hypothalamus which is a small lobe located right in the middle of your brain.

When your body is heated up, it is the hypothalamus that regulates it. But when your body is invaded by a fever-producing agent, called a pyrogen, it alarms your body and evokes a series of defensive mechanisms to fight the assault.

You can say prostaglandins, leukotrienes, and histamine, along with white blood cells and mast cells, are your body’s weapons of mass destruction that do not let invasive organism take over. They make your body an unfit and hostile place for microorganisms to thrive.

However, in the war against bacteria or other pathogens, these take quite a bit of a toll on your body as well. Amidst the maniacal battle, your body has to brave fever, pain and inflammation.

Acetaminophen suppresses PE2 and regulates your body temperature. So, apparently both acetaminophen and ibuprofen do their work well and deserve good grading.


  • Acetaminophen: 1 Ibuprofen: 01

Which Is A Better Anti-Inflammatory Agent: Acetaminophen Vs Ibuprofen

Of course ibuprofen.

  • If you have sinusitis or muscle soreness, you better pop an ibuprofen.
  • If you have an inflamed elbow, you’re better off with a bottle of Advil.
  • Advil is often prescribed in arthritic patients owing to its anti-inflammatory actions.
  • It is also recommended in sports injuries and spinal pain (backache).

A 2015 review published in BMJ found ibuprofen to be absolutely superior over acetaminophen when it comes to treating osteoarthritis of hip and knee and lower back pain.

But you cannot completely write off acetaminophen as an anti-inflammatory drug, although admittedly the action is subtle. Some studies have found acetaminophen to be effective against ankle sprains and other similar swellings that are coupled with pain.

If you are wondering why acetaminophen lacks anti-inflammatory properties despite being strikingly similar to other NSAIDs, the difference narrows down to its chemical structure.

Acetaminophen lacks a carboxylic acid (-COOH) group which chiefly accounts for anti-inflammatory effect and is present in all NSAIDS. So, it’s clear, when it is swelling you are dealing with, you need Advil, not Tylenol.


  • Acetaminophen: 0 0 Ibuprofen: 01

Which Is A Better Analgesic? Acetaminophen Or Ibuprofen

Both are! Acetaminophen is the second oldest pain killer in the world than gained a quick popularity and acceptance. First was, of course, everyone’s favorite – aspirin.

Acetaminophen is a first-line drug for pain; it is even prescribed in cancer patients, but opioid analgesics are preferable.

Ibuprofen, on the other hand, is the second youngest NSAID. Both Acetaminophen and ibuprofen are OTC drugs.

Ibuprofen is employed in all those conditions where swelling accompanies the disease such as:

  • Dental conditions involving swollen gums, toothache
  • Tonsillitis
  • Sprains or bruises associated with swelling
  • Osteoarthritis
  • Rheumatoid arthritis
  • Post-surgical inflammation
  • Period cramps

So which one is superior when it comes to painkilling?

If your pain is accompanied by swelling, as it usually is, such as swollen ankle, Advil will work better. If it’s just a headache or other pain unaccompanied by swelling, acetaminophen is your best friend.


  • Acetaminophen: 01 Ibuprofen: 01

Which Is A Better Anti-Fever Drug?

If you are trying to bring fever down, either medicine will work but some comparative studies have found Advil to have a slight edge over Tylenol.

A meta-analysis study published in JAMA Paediatrics  states that though both drugs are similar in efficacy and safety regarding analgesic and antipyretic (fever reducing) activity, ibuprofen has an edge over acetaminophen as an anti-pyretic. Moreover, ibuprofen was also found to be more effective in relieving pain following tooth extraction and during sore throat.

But the slight edge of ibuprofen does not negate the antipyretic effect of acetaminophen which remains the number #1 choice when it comes to ameliorating fever. Equal marks go to both.


  • Acetaminophen: 01 Ibuprofen: 01

Which One is Generally Safer? Acetaminophen Or Ibuprofen

Acetaminophen: Generally, acetaminophen is very well tolerated and is associated with less gastrointestinal side effects in comparison to NSAIDS. Even if taken in higher amounts, acetaminophen is associated with less hazard potential and over-dosage with up to 10 pills of 325mg or 6 extra–strength pills is permissible by the US Food and Drug Administration (FDA).

However, in certain cases, overdoses of acetaminophen can produce nausea and vomiting and acute liver failure. The FDA has given directions that the dosage of acetaminophen must not exceed 650 mg at a given time; earlier the maximum limit was 1000 mg.  The purpose of limiting maximum dose is to reduce incidence of liver failure caused by acetaminophen which might otherwise prove fatal in case of poisoning.

The FDA has also imposed a restriction that combination preparations   must not exceed 325 mg of acetaminophen in the product.

Moreover, opioid analgesics and acetaminophen combination in a single product is banned. In case of over doses, the foremost measure to be taken is to remove or excrete the drug from the body as soon as possible by inducing vomiting and immediately admitting the patient to the emergency. The antidote for acetaminophen  is N-acetyl cysteine .

Ibuprofen: Long-term use of I ibuprofen can  cause gastrointestinal irritation and stomach bleeding on long term use. In ulcer patients, high doses  should be avoided since  they  worsen the condition .

Ibuprofen also possesses a significant potential to induce acute kidney failure and therefore should be used with caution in renal impairment. Moreover, patients with cardiac diseases are also cautioned regarding its use since it may cause sudden stroke or heart failure or increase the risk on long–term use.

The drug is also forbidden in patients that have been subjected to by-pass surgery or are planning to undergo such a surgery.

However, both drugs should be avoided in case of alcohol consumption and ibuprofen requires cautionary measures when a patient is on polypharmacy, i.e., using more than one medicine.

If  the patient is concurrently taking steroids, anti-coagulants /  blood thinners or other NSAIDS ,then caution is advised. Moreover, elderly above the age of sixty years are at increased risk of stomach bleeding and ibuprofen also reduces the cardio-protective effect of aspirin.

To conclude the subject,  acetaminophen is safer than ibuprofen because its side effects are not only fewer but are also less severe than those of ibuprofen.

Howevr, every medicine has its pros and cons and the appropriate manner regarding any drug use is to use it rationally and self–medication in any condition should be denounced or discouraged.


  • Acetaminophen: 01 Ibuprofen: 00

 Which One Is Safer Children And Pregnant Women?

Acetaminophen: Despite lacking an edge over ibuprofen, acetaminophen is safer in children.

Acetaminophen is the most frequently employed analgesic in pediatrics or children below 12 years of age and is also prescribed even during pregnancy and breast feeding. It is included in World Health Organization (WHO) Model List of  Essential Medications.

Ibuprofen: Ibuprofen’s use during pregnancy has been shown to be associated with abortion or miscarriage and the drug therefore, is not prescribed during pregnancy.


  • Acetaminophen: 01 Ibuprofen: 00

Is Acetaminophen Safe In Asthmatics?

However, despite being considered safe in children, here is one condition where ambiguity lies regarding acetaminophen safety and that is asthma. Studies in asthmatics, especially those concerned with children have documented that acetaminophen is responsible for aggravating the exacerbations of asthma in pediatrics.

For this reason, physicians do not recommend acetaminophen in asthmatic children but alternatives such as ibuprofen (Advil, Motrin) or other analgesics may be employed.

However, these findings also hold truth for adults as well, as acetaminophen is  not prescribed in adult asthmatics either . The perception is supported by various observational studies that indicate that there exists a correlation between acetaminophen use and exacerbations of asthma attacks in asthmatics.

To confirm or validate such findings, a  randomized ,double-blind study has been recently published in The New England Journal of Medicine (NEJM), which was carried out as a prospective trial at  18 locations  in United states. The study was funded by the National Institutes of Health and is registered as AVICA Clinical Trial.

The study engaged 300 children aged between 12 to 59 months (1-5 years). All study participants were classified as suffering from mild but persistent asthma.  The children were categorized as control and treatment group.

Each  group was to be dispensed either acetaminophen or ibuprofen for fever and pain along with the standard asthma therapy which included  monteleukast, glucocorticoids and cromolyn in case  an asthma attack occurs .The duration of study was 48 weeks.

The study found that acetaminophen was as safe in asthmatic children as ibuprofen and that patients in acetaminophen group experienced no exacerbations or aggravation of asthma symptoms.

Moreover, there was no difference in the number of asthma free days between acetaminophen group and ibuprofen group. This means that patients who took acetaminophen did not experience less asthma-free days as compared to ibuprofen group.

Similarly, the frequency of albuterol inhaler use  was also similar in both the groups or there was no significant difference  and lastly the patients in acetaminophen group did not experience an increase in emergency visits to the hospital due to acetaminophen use.


  • Acetaminophen: 01 Ibuprofen: 01

Ibuprofen And Acetaminophen: Effects On Blood Pressure And Hypertension

Ibuprofen: All NSAIDs, including ibuprofen, have a tendency to raise blood pressure even at normal doses, i.e., those required to abate pain and inflammation, and can, therefore, increase cardiovascular risk.

Furthermore, they can reduce the efficiency of antihypertensive drugs except for calcium channel blockers (CCBs). This is due mainly to the inhibitory effects of NSAIDs on COX-2 enzymes in kidney which reduce sodium excretion.

Caution is recommended with ibuprofen. It is better that you use acetaminophen.

Acetaminophen: Acetaminophen, too, has been found to increase BP in both hypertensive and normotensive patients but the risk lesser than that of NSAIDs. Moreover, definitive evidence of acetaminophen toxicity in hypertension is limited.


  • Acetaminophen: 01 Ibuprofen: 00

Nonetheless, it is better that you consult your doctor before choosing either.

Effects On Period Cramps

This is easy; all girls of reproductive age can easily vouch for ibuprofen.

Ibuprofen: Saves the day for millions of girls doubling-over with monthly menstrual cramps. The culprit behind painful period cramps is none other but prostaglandins.

Prostaglandins are not that bad though, they just sometimes overdo, whatever they are doing in our body. They regulate smooth muscle contraction in the body and as they do so, they contract uterus (made up of smooth muscles) and helps shed its lining. The more prostaglandins there are in your body, the more strongly your uterus will contract and the more intense your cramps will be.

Period clamps also arise when there is reduced or lack of blood supply to uterus. When the uterus contracts, it clamps down its blood supply leading to cramps. Period cramps can be extremely painful for women suffering from endometriosis and fibroids.

And this is where ibuprofen kicks in – by successfully inhibiting COX enzymes, it prevents the formation of prostaglandins ultimately ameliorating muscle cramps. It also relaxes smooth muscles and increases blood supply.

Ibuprofen clearly wins here.


  • Acetaminophen: 00 Ibuprofen: 01

Pregnancy Category

Pregnancy is a condition where caution is required for even the safest drug. As far as acetaminophen status during pregnancy is concerned, it is categorized as pregnancy category B in all three trimesters whereas ibuprofen is associated with more risk factor and is categorized as pregnancy category B during 1st and 2nd trimesters but bears category D during 3rd trimester.


First trimester:           Acetaminophen: 01                            Ibuprofen: 01

Second trimester:       Acetaminophen: 01                            Ibuprofen: 01

Third trimester:          Acetaminophen: 01                            Ibuprofen: 00

Monotherapy Or Combination Therapy: Which To Opt For?

Another randomized, double blind study, published in  JAMA Paediatrics searched answer regarding the dosage regimen. The study  was executed to find answers regarding what kind of therapy is more efficacious: monotherapy or combined therapy administered as alternating therapy .

The study was conducted in  pediatric ambulatory centers in central Israel that engaged 464 infants suffering from fever, aged between 6 to 36 months  .The results showed that combined therapy administered as alternating therapy is more efficacious in comparison to the monotherapy.

Difference Between Acetaminophen And Ibuprofen?

By now you must have pretty much got a clear idea as to which drug is better for you if you have fever and pain. Here are the results:

  • Acetaminophen: 10/12 Ibuprofen: 08/12

But before you grab and empty the Tylenol bottle, do remember the drug has its limitations. If it is inflammation you are dealing with and provided you do not have allergy or underlying kidney complications, then ibuprofen will give you best bang for your buck.

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