PURPOSE: To compare the safety and efficacy of orally administered clarithromycin, a new macrolide antimicrobial, and amoxicillin in the treatment of patients with acute maxillary sinusitis. PATIENTS AND METHODS: One hundred forty-two consecutive outpatients treated at four primary care centers for acute maxillary sinusitis were randomly assigned to receive oral clarithromycin (500 mg twice daily) or oral amoxicillin (500 mg three times daily) for 7 to 14 days. Clinical and roentgenographic responses to the antibiotic therapy were determined within 48 hours after the last dose and 6 weeks later. RESULTS: The success rates of clarithromycin and amoxicillin were comparable. A clinical success rate of 91% and a roentgenographic success rate of 78% were achieved in the clarithromycin group at the final visit; comparable results for the amoxicillin group were 89% and 92%, respectively. Differences between the two groups were not statistically significant (P = .766 and .064, respectively). No serious adverse events were reported, although both drugs caused mild gastrointestinal distress. Dropout rates were low in both groups: 3% for clarithromycin and 4% for amoxicillin. No clinically significant changes in laboratory studies were observed in either group. CONCLUSION: Clarithromycin twice daily is effective and well tolerated in patients with acute maxillary sinusitis.