BACKGROUND: A combination of analgesic drugs with different pharmacologic properties may be more effective, with fewer adverse events, than either agent used alone. OBJECTIVE: This study assessed whether the combination of acetaminophen and ketoprofen is more effective and better tolerated than either drug used alone in treating postoperative pain. METHODS: This single-dose randomized, double-blind, active- and placebo-controlled study was conducted at the Finnish Student Health Service, Oulu, Finland. Patients aged 18 to 40 years with moderate or severe pain (>or=3 on a numerical rating scale [NRS] of 0-10) after surgical removal of impacted third molars were randomly assigned to receive one of the following drugs in single oral doses: ketoprofen 100 mg + acetaminophen 1000 mg, ketoprofen 100 mg, acetaminophen 1000 mg, or placebo tablets. Effectiveness was assessed by the onset of analgesia, pain intensity difference (PID) from baseline, sum of PID (SPID), and duration of analgesic effect. Patients rated pain intensity on the NRS at rest and on dry swallowing. Onset of pain relief was measured using time to PID in >or=1 category at rest or on dry swallowing (PID >or=1). Patients recorded the occurrence of adverse events and the supplemental consumption of rescue medication (ibuprofen). RESULTS: The study included 76 patients, accounting for 78 cases (2 patients were operated on twice and were assessed as 4 individual patients) (59% women, 41% men; mean age, 22.8 years; white race, 100%; and mean weight, 68.3 kg). At 1.5 hours, mean SPIDs at rest and on swallowing were significantly greater in the combination group than in the acetaminophen, ketoprofen, and placebo groups (all, P or=1) at rest and on swallowing were significantly less in the combination group than the acetaminophen, ketoprofen, and placebo groups (all, P