The antihypertensive efficacy and tolerability of candesartan cilexetil (CAND), a potent, selective angiotensin II (AT1) receptor blocker, vs amlodipine (AML), a potent, dihydropyridine calcium channel blocker, were evaluated in patients with mild (JNC VI, Stage 1) hypertension. In this 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study, a total of 251 adult patients (45% female, 16% black) with sitting diastolic blood pressures (DBP) of 90 to 99 mmHg, inclusive, during a 4- to 5-week placebo run-in period were randomly assigned to treatment with CAND 16 mg or AML 5 mg, once daily. After 4 weeks of double-blind treatment, patients were uptitrated to CAND 32 mg or AML 10 mg, once daily. The primary efficacy endpoint was the reduction in trough (24 ± 3 hours after dose) DBP at Week 8. The primary pre-specified tolerability endpoint was peripheral edema, defined as pitting edema that was evident in the morning or afternoon after applying gentle pressure for 5 seconds to the pedal, ankle, and/or pre-tibial regions. There were no significant differences between the CAND (16 ⇒ 32 mg) and AML (5 ⇒ 10 mg) regimens for reducing BP; changes in mean trough sitting systolic/DBP were −15.2/−10.2 mmHg vs −15.4/−11.3 mmHg, respectively (p = 0.88/0.25). Overall, 79% of patients on CAND were controlled (DBP <90 mmHg) compared with 87% on AML. Ratios of trough to peak (6 ± 2.5 hours after dose) effect on DBP were 1.0 for CAND vs 0.95 for AML, indicating persistence of BP reduction for a full 24 hours for each drug with once daily dosing. A total of 3.3% of patients on CAND discontinued treatment prematurely, compared with 9.4% of patients on AML, including 2.4% vs 4.7% for adverse events, respectively. Peripheral edema occurred with significantly (p = 0.005) greater frequency in patients on AML (22.1%: mild 8.7%, moderate 11.8%, severe 1.6%) vs patients on CAND (8.9%: mild 8.1%, moderate 0.8%). Candesartan cilexetil and amlodipine are both highly effective in controlling blood pressure in patients with mild hypertension. Candesartan cilexetil offers efficacy similar to amlodipine with significantly less peripheral edema.