Yes, many people can safely take Tylenol and Advil together to treat short-term pain or fever. But before combining them, ask yourself: Do I really need both?
Gina Jansheski, M.D., is a pediatrician with 22 years of practice experience. Dr. Jansheski completed her medical education at the University of Arizona College of Medicine, followed by a pediatric residency and a one-year fellowship in Developmental and Behavioral Pediatrics. She served as the medical director of Tucson Pediatric Hospitalists, providing pediatric hospice and palliative care services.
Chances are you’ve reached for acetaminophen (Tylenol) or ibuprofen (Advil, Motrin), two of the most common over-the-counter (OTC) pain relievers, at some point in your life. These medications can alleviate pain and fever, and ibuprofen is also helpful for lowering inflammation.
But is taking acetaminophen and ibuprofen together more effective than taking one alone? And is it safe? Sometimes, yes. Combining or alternating these two OTC medications may provide stronger pain and fever relief than taking either alone. But to avoid harm, it’s important to get the dosing schedule right.
Yes, many adults and children can safely take acetaminophen and ibuprofen at the same time, or alternate them every few hours. Whether this is the right choice for you depends on several personal factors like age, other medications you’re taking and any health conditions you have.
Even after decades of use, it is still unclear exactly how acetaminophen works for treating pain. We know it mostly works in the brain and spinal cord, affecting chemicals that contribute to pain and fever, like prostaglandins, cannabinoids and serotonin.
Ibuprofen also blocks the production of prostaglandins, chemical compounds that contribute to fever, pain and inflammation. But ibuprofen acts in the brain and at the site of injury and inflammation. This is what makes ibuprofen an effective anti-inflammatory, while acetaminophen is not. Ibuprofen belongs to a group of medications called nonsteroidal anti-inflammatory drugs (NSAIDs). Other NSAIDs include naproxen (Aleve, Naprosyn), aspirin and meloxicam.
Because acetaminophen and ibuprofen work differently, taking them together may provide more substantial relief than using either medication alone, says Xueduan (Ray) Liu, PharmD, CSP, a pharmacist at the University of California, Los Angeles. And since these medications don’t interact with each other directly, combining them is usually safe, as long as you use the correct dose and don’t have health reasons to avoid either medication.
Combining these two medications can sometimes give better pain or fever relief than taking either alone. It may also allow you to use lower doses, says Roxann Engle, D.O., a family medicine physician at University of California, Irvine Health. And if your healthcare provider recommends taking acetaminophen and ibuprofen at the same time, they’re now available OTC as a single pill, which can simplify dosing.
Alternating acetaminophen and ibuprofen can get complicated, Dr. Engle notes. For fever in children, she often recommends alternating the two every three hours so one is always working at its peak. But it’s crucial to track doses carefully to avoid taking too much by inadvertently repeating one. For ongoing conditions like chronic pain, she usually suggests taking them together instead, which makes the schedule easier to follow.
Another possible disadvantage is that combining them exposes you to the potential side effects of each, notes Dr. Liu. While these medications are often well-tolerated, potential side effects include nausea or stomach upset, which are commonly associated with ibuprofen. Acetaminophen is generally safe and free of side effects when taken at recommended doses, though excessive or long-term use has been linked to liver injury.
Many studies have examined the combination of acetaminophen and NSAIDs like ibuprofen, including a 2025 review of more than 75 studies. Much of this research involved short-term use, tested only one or a few doses, and included a small number of participants.
Below, we’ll dive into the details of the evidence for combining acetaminophen and ibuprofen, but here are some key takeaways:
In a review of three studies involving more than 1,600 participants, two trials found that the combination of ibuprofen and acetaminophen provided greater pain relief after dental surgery than placebo (a pill with nothing in it), and one trial found it was more effective than ibuprofen alone.
Other small studies examining pain after anterior cruciate ligament (ACL) knee surgery, acute muscle pain after injury and acute non-injury-related lower back pain found that combining acetaminophen and ibuprofen wasn’t more effective than ibuprofen alone.
Some studies also showed that combining acetaminophen and ibuprofen for short-term pain treatment may decrease opioid use. However, a study of over 500 people found that ibuprofen alone may be as effective as combination treatment at reducing opioid use in the first 24 hours after hip replacement surgery.
Research on combining ibuprofen and acetaminophen in adults with fever is limited. The evidence is more robust in children.
A review of 31 randomized controlled trials, including more than 4,000 children, found that ibuprofen plus acetaminophen was more effective than acetaminophen alone at reducing fever. But ibuprofen alone (7.5 mg/kg to 10 mg/kg per dose) was as effective as the combination.
In this review, researchers found that in the first few hours of treatment, children taking both medications at once fared slightly better than those who alternated them. But by six hours, there was no difference between these dosing methods.
Importantly, when comparing combination treatment to using one medication alone, temperature reduction differences are often modest. So even if the results of combination treatment appear better on paper, the temperature reduction might not be large enough to make a noticeable difference in how your child feels.
Whether combining acetaminophen and ibuprofen is right for you depends on several factors. Often, checking in with a healthcare provider is the best first step. Combining these medications isn’t one-size-fits-all, says Dr. Engle. Here are key questions to consider:
If you’ve decided to take acetaminophen and ibuprofen together, here are practical tips to do it safely:
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