Unsatisfactory blood pressure (BP) control in the treated hypertensive patient is largely related to poor compliance with antihypertensive drug regimens. The aim of the present study was to prospectively evaluate the rate of persistence on treatment and the extent of BP control in 301 elderly, uncomplicated grade I or II hypertensive patients randomly allocated to monotherapy with angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), beta-blockers, angiotensin II receptors (ARBs), or diuretics according to an open-label single-blind study design. After 24 months, the percentage of patients continuing their initial therapy was higher in those treated with ARBs (68.5%) and ACE inhibitors (64.5%) and lower in patients taking diuretics (34.4%; P<.01). The logistic regression model using ARBs as reference term showed that patients treated with ACE inhibitors (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.79-0.99) or CCBs (OR, 0.76; 95% CI, 0.54-0.85) were more likely to continue their initial antihypertensive therapy when compared with those treated with beta-blockers (OR, 0.67; 95% CI, 0.57-0.79) or diuretics (OR, 0.56; 95% CI, 0.38-0.84). The average systolic and diastolic BP decrease was greater in patients treated with ARBs (-11.2+/-4/-5.8+/-2 mm Hg), ACE inhibitors (-10.5+/-4/-5.1+/-2 mm Hg), and CCBs (-8.5+/-3/-4.6+/-2 mm Hg) and lesser in those treated with diuretics (-2.3+/-4/-2.1+/-3 mm Hg, P<.05) and beta-blockers (-4.0+/-2/-2.3+/-2 mm Hg; P<.05). The study confirms the importance of persistence with treatment for the effective management of hypertension in clinical practice.