OBJECTIVES: Drug regimen complexity, medication type, patient characteristics, and comorbidities have been associated with antihypertensive medication adherence. This study evaluated the association of adherence with demographic (age and gender), clinical (blood pressure control and comorbidities), and medication (type and number prescribed) characteristics. METHODS: Electronic medical records from Central Texas Veterans Health Care System were extracted for veterans receiving at least 2 antihypertensive prescriptions within 1 year between 1995 and 2003. Adherence rate (AR) was calculated for each treatment episode. Multiple regression analysis was employed and a p-value of 0.01 was chosen. RESULTS: Study participants’ (N=34,719) mean AR was 0.95±0.28, ranging from 0 to 1.5. Participants were predominantly males (95.3%), with an average age of 62.8±12.6 years. More than two-thirds (68.3%) of patients’ treatment episodes (N=56,875) were part of multiple therapy. Uncontrolled blood pressure was prevalent (75.8%), and many patients had diabetes (20.5%), cardiovascular complications (22.3%), and hyperlipidemia (30.7%). Multiple regression analysis showed that older patients on multiple therapies had significantly higher AR's. Uncontrolled blood pressure, type-two diabetes, and hyperlipidemia were also associated with higher AR; whereas cardiovascular complications and type-one diabetes were associated with lower AR. Controlling for the above variables, adherence was significantly higher for angiotensin converting enzyme inhibitors (ACEI) and lower for angiotensin II receptor blocker, beta blocker, diuretic, other (including aldosterone receptor blockers, central alpha agonists, diazoxide, and peripheral vasodilators) and pre-formulated combination therapies. While the model demonstrated overall significance (p<0.0001), it only explained 2.8% of the variance. CONCLUSIONS: The study showed that patient, clinical, and medication characteristics were associated with medication adherence. Patients who had more comorbidities and those on multiple therapies seemed to have higher adherence levels. Nevertheless, our results need to be interpreted with caution, due to the small proportion of variance explained by the model and the range of adherence observed.