A meta-analysis was conducted to determine whether prophylactic systemic antibiotics prevent infection in patients with nonbite wounds that are managed in the emergency department (ED). A literature search was performed to identify published, randomized trials of prophylactic antibiotics for nonbite wounds. Blinded review of trial methods was used to select trials that randomly assigned patients to antibiotic or control groups and analyzed results by intention to treat. Of 9 randomized trials, 7 (with 1,734 study subjects) were accepted for analysis. The odds ratio for infection in treated patients compared with controls was used as the measure of effect, and a summary odds ratio was calculated. Patients treated with antibiotics had a slightly greater incidence of infection compared with untreated controls: odds ratio 1.16 (95% confidence interval [CI] 0.77 to 1.78). Even among patients treated with a penicillinase-resistant antibiotic (5 trials with 1,204 patients), there was no benefit from treatment; odds ratio 1.00 (95% CI 0.59 to 1.71). In conclusion, there is no evidence in published trials that prophylactic antibiotics offer protection against infection of nonbite wounds in patients treated in EDs.