OBJECTIVE: To evaluate the effectiveness and safety of short-course antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed and the Cochrane Central Register of Controlled Trials using a structured search strategy. The last date either database was accessed was November 14, 2007. We included RCTs that involved patients of any age with GAS tonsillopharyngitis, comparing short-course (< or =7 days) vs long-course (at least 2 days longer than short-course) treatment with the same antibiotics. The primary analysis compared 5 to 7 days with 10 days of treatment, using a random effects model. RESULTS: Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. In the primary analysis, microbiological eradication rates of GAS were inferior for short-course vs long-course treatment (8 RCTs, 1607 patients; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.32-0.74). This association was noted with penicillin V treatment (3 RCTs, 500 patients; OR, 0.36; 95% CI, 0.13-0.99) but was nonsignificant with cephalosporin treatment (4 RCTs, 1018 patients; OR, 0.62; 95% CI, 0.38-1.03). Microbiological eradication was less likely with short-course treatment in trials involving primarily children and adolescents (aged <18 years) (6 RCTs, 1258 patients; OR, 0.63; 95% CI, 0.40-0.98). Clinical success was inferior in patients who received short-course treatment (5 RCTs, 1217 patients; OR, 0.49; 95% CI, 0.25-0.96). Adverse events did not differ between compared groups. The above associations were consistent in the analyses involving all included RCTs. CONCLUSION: Short-course treatment for GAS tonsillopharyngitis, particularly with penicillin V, is associated with inferior bacteriological eradication rates.