OBJECTIVES: A previous study conducted by the authors indicated that calcium channel blockers, ACE inhibitors, beta blockers and diuretics were the four most commonly used therapeutic classes of antihypertensives in a commercial HMO population. The objective of this study was to compare adherence between these four classes of antihypertensives. METHODS: This study was a retrospective pharmacy claims database analysis. All members evaluated had a diagnosis of hypertension, received at least two prescriptions for an antihypertensive drug, and were continuously enrolled during the one-year study period. The average medication possession ratio (MPR) was used as a primary adherence indicator. An analysis of covariance was conducted to determine if differences in the mean MPR existed based on the antihypertensive therapeutic class. Previous research in this population indicated that age, units per day of the drug, number of concurrent medications and total days supply were significant predictors of adherence. These factors were for in this analysis. RESULTS: The average MPR was evaluated for 1637 members meeting the inclusion criteria. The average age of the members was 52.85 year and 53.63% were female. The mean (S.D.) MPR for the therapeutic classes were: ACE inhibitors 0.8626 (0.2370), beta-blockers 0.8534 (0.2288), calcium channel blockers 0.8770 (0.2078), diuretics 0.8291 (0.2705). The MPR were significantly higher in members on calcium channel blockers versus diuretics (mean difference = 0.0524, 95% CI = 0.0140 - 0.0907, p <0.005) and ACE inhibitors versus diuretics (mean difference = 0.0473, 95% CI = 0.0139 - 0.0808, p <0.005). There were no significant differences in adherence between the other classes of antihypertensives. CONCLUSIONS: After controlling for significant predictors of adherence, the MPR for members on calcium channel blockers and ACE inhibitors were significantly higher than for those patients on diuretics. These results may have implications for the effectiveness of different therapeutic classes of antihypertensives in blood pressure control.