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To examine whether short-term use of azithromycin increases the risk of sensorineural hearing loss (SNHL) in adults with uncomplicated infections.A retrospective cohort study using Medicaid claims data, 1999 to 2010.Adults (18–64 years old) who had continuous enrollment in Medicaid for the 12 months (baseline) before the date of first dispensation (index date) of oral azithromycin or amoxicillin ± clavulanate for uncomplicated infections.We operationalized sensorineural hearing loss (SNHL) by a charge for audiometry and followed by a diagnosis of SNHL within 30 days.We adjusted for the baseline covariates through propensity score matching. Adults were followed for up to 120 days after the index date. The hazard of SNHL in azithromycin-exposed adults was compared with those who had amoxicillin ± clavulanate using a Cox proportional hazard model. We performed several sensitivity analyses by varying the follow-up time, SNHL definition, adjusting for cumulative antibiotic use, and switching exposure status during the follow-up period.A total of 493,774 patients entered the study cohort. The unadjusted incidence rates of SNHL were 38 and 41 cases per 10,000 patient-years following exposure to azithromycin and amoxicillin ± clavulanate, respectively. The adjusted (matched) hazard ratio (HR) of SNHL for azithromycin versus amoxicillin ± clavulanate was 0.91 (95% confidence interval [CI], 0.77–1.07). The sensitivity analyses findings were consistent with the primary analysis.Azithromycin short-term use was not associated with an increased risk of SNHL in comparison to amoxicillin ± clavulanate.