The calcium channel blocker amlodipine and angiotensin ll receptor blocker losartan, with or without hydrochlorothiazide (HCTZ), were compared for the treatment of mild to moderate hypertension in a multicenter, double-blind, parallel-group clinical trial. Following a 2-week placebo run-in, 440 adults (45–80 years old) were randomized to receive either amlodipine 5 mg once daily or losartan 50 mg once daily. Patients who failed to meet the sitting diastolic blood pressure (BP) reduction goal of 90 mm Hg after 6 weeks had their dose increased to 10 mg amlodipine or had 12.5 mg of HCTZ added to the losartan 50 mg. A total of 42.3% of losartan and 43.6% of amlodipine subjects achieved a diastolic BP of 90 mm Hg at initial dose (low dose). Of those who completed treatment at the low dose, 71% of the amlodipine- and 81% of the losartan-treated patients met BP goal. This difference was not statistically significant. Of those who received a dosage adjustment, a significantly greater percentage of amlodipine-treated patients (59%) than losartan/HCTZ-treated patients (42%) reached BP goal at the last visit (p=0.009). Including both high- and low-dose subjects, 63.8% of amlodipine and 55.1% of losartan patients achieved a diastolic BP of 90 mm Hg at the last maintenance visit; this difference was not significant (p=0.07). Overall, reductions in mean sitting BP from baseline to the end of treatment were significantly greater in the amlodipine group than in the losartan group for both diastolic BP (−12.6 vs. −10.3 mm Hg; p=0.002) and systolic BP (−16.1 vs. −13.7 mm Hg; p=0.018). Additionally, the response rate was significantly greater after treatment with amlodipine than with losartan in African Americans (62.5% vs. 41.4%; p=0.033) and the other mostly Hispanic patients (67.7% vs. 53.5%; p=0.039). Both treatment groups showed significant reductions from baseline in 24-hour ambulatory BP at the end of treatment, with no difference between them. Adverse events were consistent with the safety profile of each drug. It is concluded that, while both amlodipine and losartan demonstrated a significant benefit for the treatment of mild to moderate hypertension, there were greater reductions in most BP measurements following treatment with amlodipine in comparison to losartan with or without HCTZ.