Comparison of the clinical efficacy of naproxen, associated or not with esomeprazole, in the control of pain, swelling and trismus in lower third molar removal Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to manage postoperative pain and inflammation in patients after oral and maxillofacial surgery, yet they are often associated with gastrointestinal problems. Recently the NSAID naproxen was introduced in combination with esomeprazole, a proton pump inhibitor that reduces stomach acid formation, in an effort to assuage these side effects. Using a double-blinded randomized crossover design, this study aimed to evaluate, for the first time, acute postoperative pain management in 46 volunteers who consumed a tablet of either naproxen (500 mg) with esomeprazole (20 mg) (NE) or only naproxen (500 mg) every 12 hours for 4 days after extractions of the two lower third molars, in two different appointments. Female volunteers reported significantly more pain at 1, 1.5, 2, 3 and 4 hours after surgery and also consumed their first rescue medication (acetaminophen) at a time significantly earlier when consuming NE when compared to naproxen (3.7 hours and 6.7 hours, respectively). No significant differences were found in the males between each research group. In conclusion, naproxen improved acute postoperative pain management when compared to NE in women although, throughout the entire study, pain was mild after the use of both drugs in both men and women with pain scores on average well below 40 mm on the VAS.