OBJECTIVES: Clarithromycin and amoxicillin/clavulanate (A/C) are first line antibiotics used to treat uncomplicated acute rhinosinusitis (ARS). This study examined the efficacy of clarithromycin and A/C for the treatment of ARS relative to the patient's quality of life (QOL). STUDY DESIGN: Twenty-two patients with uncomplicated ARS were randomly assigned treatment (single blinded relative to the investigator) using clarithromycin or A/C. Patients underwent assessment to confirm the diagnosis and treatment outcome at the initial screening and on completion of antibiotics (diagnosis + 14 days and 28 days). QOL was evaluated using the Allergy Outcomes Survey (AOS), the Rhinoconjunctivitis QOL Questionnaire (RQLQ), the Short Form 36 survey (SF-36), an instantaneous six-item Symptom Severity Survey (SSS-6), and a Visual Analogue Scale (VAS). Surveys were completed at the time of diagnosis, on completion of antibiotics, and at 28 days after diagnosis. RESULTS: Twenty patients completed the study. The SSS-6 and the RQLQ demonstrated significant improvement for all patients at week 4 (P =.002 and P =.003, respectively). The SSS-6 demonstrated significant improvement for clarithromycin at 14 days (P =.02) and at 28 days (P =.029), whereas A/C patients demonstrated significant improvement in symptoms only at 28 days (P =.046). The RQLQ, which reflects the previous 2 weeks, demonstrated significant improvement for the A/C patients at 28 days (P =.01). The Allergy Survey, the SF-36, and the VAS failed to demonstrate significant improvement in the combined data analysis. CONCLUSIONS: Clarithromycin and A/C were equally effective in treating ARS. The clarithromycin patients felt better more rapidly (at 14 days), but both groups of patients had long-term improvement in symptoms at 28 days.