BACKGROUND: The purpose of this study was to identify potential health system solutions to suboptimal use of antihypertensive therapy in a diverse cohort of patients initiating treatment. METHODS: Using a hypertension registry at Kaiser Permanente Northern California, we conducted a retrospective cohort study of 44 167 adults (age, >/=18 years) with hypertension who were new users of antihypertensive therapy in 2008. We used multivariate logistic regression analysis to model the relationships between race/ethnicity, specific health system factors, and early nonpersistence (failing to refill the first prescription within 90 days) and nonadherence (<80% of days covered during the 12 months following the start of treatment), respectively, controlling for sociodemographic and clinical risk factors. RESULTS: More than 30% of patients were early nonpersistent and 1 in 5 were nonadherent to therapy. Nonwhites were more likely to exhibit both types of suboptimal medication-taking behavior compared with whites. In logistic regression models adjusted for sociodemographic, clinical, and health system factors, nonwhite race was associated with early nonpersistence (black: odds ratio, 1.56 [95% CI, 1.43-1.70]; Asian: 1.40 [1.29-1.51]; Hispanic: 1.46 [1.35-1.57]) and nonadherence (black: 1.55 [1.37-1.77]; Asian: 1.13 [1.00-1.28]; Hispanic: 1.46 [1.31-1.63]). The likelihood of early nonpersistence varied between Asians and Hispanics by choice of first-line therapy. In addition, racial and ethnic differences in nonadherence were appreciably attenuated when medication co-payment and mail-order pharmacy use were accounted for in the models. CONCLUSIONS: Racial/ethnic differences in medication-taking behavior occur early in the course of treatment. However, health system strategies designed to reduce patient co-payments, ease access to medications, and optimize the choice of initial therapy may be effective tools in narrowing persistent gaps in the use of these and other clinically effective therapies.