OBJECTIVE: To summarize studies testing the efficacy and safety of single-dose acetaminophen and ibuprofen for treating childrenʼs pain or fever. DATA SOURCES: Reports were gathered by searching computerized databases (from their inception through May 2002) and registries, relevant journals, and bibliographies of key articles. STUDY SELECTION: Seventeen blinded, randomized controlled trials with children (<18 years) receiving either drug to treat fever or moderate to severe pain. DATA EXTRACTION: Under a fixed-effects model, outcome measures for an initial single dose of ibuprofen vs acetaminophen were the risk ratio for achieving more than 50% of maximum pain relief, effect size for febrile temperature reduction, and risk ratio for minor and major harm. DATA SYNTHESIS: Ibuprofen (4–10 mg/kg) and acetaminophen (7–15 mg/kg) showed comparable efficacy (3 pain relief trials; 186 children). The risk ratio point estimates was 1.14 (95%confidence interval [CI], 0.82–1.58) at 2 hours after receiving the dose, and 1.11 (95% CI, 0.89–1.38) at 4 hours. Ibuprofen (5–10 mg/kg) reduced temperature more than acetaminophen (10–15 mg/kg) at 2, 4, and 6 hours after treatment (respective weighted-effect sizes: 0.19 [95% CI, 0.05–0.33], 0.31 [95% CI, 0.19–0.44], and 0.33 [95% CI, 0.19–0.47]) (9 fever trials; 1078 children). For ibuprofen 10 mg/kg (acetaminophen, 10–15 mg/kg), corresponding effect sizes were 0.34 (95% CI, 0.12–0.56), 0.81 (95% CI, 0.56–1.03), and 0.66 (95% CI, 0.44–0.87). There was no evidence the drugs differed from each other (or placebo) in incidence of minor or major harm (17 safety trials; 1820 children). CONCLUSIONS: In children, single doses of ibuprofen (4–10 mg/kg) and acetaminophen (7–15 mg/kg) have similar efficacy for relieving moderate to severe pain, and similar safety as analgesics or antipyretics. Ibuprofen (5–10 mg/kg) was a more effective antipyretic than acetaminophen (10–15 mg/kg) at 2, 4, and 6 hours posttreatment.