For adults seeking care in ambulatory practices, sinusitis is the most common diagnosis treated with antibiotics. We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. Relevant studies were identified from searches of MEDLINE and EMBASE in October 1998, contacts with pharmaceutical companies and bibliographies of included studies. Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes for acute maxillary sinusitis. Additional criteria were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement and a sample size of 30 or more adults. Of 1784 potentially relevant studies, two or more reviewers identified 32 studies meeting selection criteria. Data were abstracted independently by 2 persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were a) clinical cure and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. Thirty-two trials, involving 7,330 subjects evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic vs. control (n=5); newer, non-penicillin antibiotic vs. penicillin class (n=10); and amoxicillin-clavulanate vs. other extended spectrum antibiotics (n=10). Most trials were conducted in otolaryngology settings. Only 5 trials described adequate allocation and concealment procedures; 10 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72, 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53), but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins vs. penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins vs. amoxicillin-clavulanate (RR for cure 1.01, 95% CI 0.97 to 1.04). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics. Relapse rates within one month of successful therapy were 5%. For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.