OBJECTIVES: Patient adherence is critical for successful management of mental illnesses. This study compares adherence rates across branded selective serotonin reuptake inhibitors. METHODS: This retrospective cohort study used an administrative database between January 1, 1999 and June 30, 2002. Adherence status was categorized into persistence, switching and discontinuation. Persistence was defined based on the days supply, with a minimum of 15 days to refill. Survival analyses were conducted. Age, gender, and co-payment were included as covariates in Cox proportional models. Sensitivity analyses were performed to determine the sensitivity of the algorithm for determining adherence. RESULTS: Compared with sertraline patients (N = 5598), those on paroxetine (N = 5204) had lower persistence rates (23.8%vs. 26.0%, P = 0.0093), higher switching (3.6% vs. 3.3%, P = 0.5076) and discontinuation rates (72.7% vs. 70.7%, P = 0.0258). Survival curves showed that the persistence rates for sertraline patients were significantly greater than for paroxetine (P <0.05, Log-Rank and Wilcoxon tests), while similar to those for citalopram patients (N = 4131). Age and gender were independent predictors of persistence, while co-payment was not. These findings were consistent across a broad variety of definitions of persistence by varying the allowed time to refill. CONCLUSIONS: Paroxetine patients were significantly more likely to discontinue therapy than either sertraline or citalopram patients.