The combined use of acetaminophen and a nonsteroidal antiinflammatory drug has been shown to provide better postoperative analgesia than either drug alone in several adult studies. However, there are no pediatric studies analyzing similar effects when the currently recommended doses of acetaminophen are used. In a double-blind, placebo-controlled design we randomized 120 children, aged 1–9 yr, undergoing orthopedic or soft tissue surgery, into 3 groups to receive either acetaminophen 60 mg/kg rectally and 40 mg/kg orally, ketoprofen 2 mg/kg IV twice, or the combination of the active drugs. The first drug doses were given at anesthetic induction and the second doses 8 h thereafter. During anesthesia all children received sevoflurane and a continuous infusion of remifentanil. Postoperative pain was evaluated by the behavioral objective pain scale (0–9) for 24 h. The rescue medication was morphine 0.05 mg/kg IV. The primary outcome variable was morphine consumption. For statistical analysis, analysis of variance, χ2 test and Kaplan-Meier survival analysis were used. Morphine requirement was less in the combination than in the acetaminophen group both in the postanesthesia care unit (2.5 ± 1.7 versus 3.9 ± 2.1 morphine doses) and during the 24-h postoperative follow-up (4.1 ± 2.5 versus 5.9 ± 2.9 morphine doses) (P < 0.05). No differences existed between the ketoprofen and the acetaminophen groups. The objective pain scale scores were lowest in the combination group both in the postanesthesia care unit and in the postoperative ward (P < 0.05). When children were divided based on their surgery, opioid requirement and pain scores were less in the combination than in the parent drug groups only after orthopedic surgery. The combination of acetaminophen 100 mg/kg and ketoprofen 4 mg/kg in a day provided better analgesia and lower pain scores after orthopedic, but not soft tissue, surgery in children.