OBJECTIVES: Acute and chronic sinusitis is the fifth most common diagnosis for which antibiotics are prescribed, accounting for direct annual costs of more than $3.3 billion in the U.S. The objective of this study was to evaluate antibiotic prescribing patterns in acute sinusitis and compare the effectiveness and associated resource utilization of azithromycin versus amoxicillin, amoxicillin/clavulanate, and clarithromycin. METHODS: Between 2/1/99 and 5/31/00, patients with an ICD-9 code for their first hospital or outpatient acute sinusitis visit receiving antibiotic therapy within 5 days of diagnosis were selected from a managed cared database and evaluated for inclusion in the analysis. Clinical outcomes and total resource utilization were assessed over a 30-day period in patients meeting eligibility criteria. Clinical outcomes were defined as: a) cured for patients receiving only one antibiotic, b) improved for patients receiving a second course of the initial antibiotic, and c) failed for patients receiving a second course of a different antibiotic or hospitalized for a respiratory tract infection. RESULTS: A total of 27,087 eligible patients received 28,537 initial antibiotic prescriptions for acute sinusitis. Azithromycin (17%) was the second most commonly prescribed antibiotic preceded by amoxicillin (31%), and followed by amoxicillin/clavulanate (12%) and clarithromycin (7%). Efficacy amongst comparators was similar; although azithromycin treated patients had the highest percentage of cures (86%) and fewest failures (9%). Amoxicillin/clavulanate (83%) had the fewest cures and clarithromycin had the most failures (11%). Azithromycin was $35 more expensive than amoxicillin with a total mean cost of approximately $141 compared to clarithromycin and amoxicillin/clavulanate, which were $80 and $89 more expensive than amoxicillin ($106), respectively. In contrast to amoxicillin/clavulanate and clarithromycin, pharmacy claims accounted for <50% of amoxicillin and azithromycin total costs. CONCLUSIONS: With comparable efficacy and resource utilization advantages versus amoxicillin/clavulanate and clarithromycin, this study suggests azithromycin was the most cost-effective brand antibiotic.