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To investigate the risk factors and comorbidities associated with ethambutol-induced optic neuropathy (EON).Using the Taiwan Longitudinal Health Insurance Database, we conducted a study within a nationwide representative cohort of patients treated with EMB. We identified 231 patients newly diagnosed with EON between 2000 and 2008, and 924 control subjects. Adjusted OR by estimating the risk of EON in relation to comorbidities and EMB prescription protocol was determined.Compared with the control group, EON patients were at risk with older age, hypertension (adjusted OR=1.62, 95% CI 1.16 to 2.26) and renal diseases (without end-stage renal diseases (ESRD), adjusted OR=2.11, 95% CI 1.02 to 4.35; with ESRD, adjusted OR=3.73, 95% CI 1.79 to 7.74). Patients with an EMB prescription duration longer than 3 months were not at elevated risk compared with those whose prescription less than 3 months (OR=1.35, 95% CI 0.99 to 1.83, adjusted for age, sex, hypertension and renal diseases). Patients whose average daily dose was greater than 1200 mg, compared with the other two groups (800∼1199 mg, less than 800 mg) were not at increased risk for EON.Age, hypertension and renal diseases are risk factors for EON in the Taiwanese population.