Hypertension is particularly prevalent in patients aged ≥65 years, those with a body mass index ≥30 kg m(-2), Blacks and those with type II diabetes. Here we report a prespecified secondary analysis of the efficacy of amlodipine (10 mg day(-1)), olmesartan medoxomil (40 mg day(-1)), a combination of the two and placebo in these subgroups. Patients were randomized to treatment for 8 weeks. The primary efficacy endpoint was the change from baseline in mean seated diastolic blood pressure (DBP). Secondary efficacy endpoints included the change from baseline in mean seated systolic BP (SBP), proportions of patients achieving BP goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes), and the number and percentage of patients achieving a range of BP targets. Safety and tolerability of amlodipine 5 and 10 mg, olmesartan medoxomil 10, 20 and 40 mg, and all possible combinations of the two were also assessed. For each prespecified subgroup, all active treatments resulted in significant BP reductions from baseline (P<0.05). The antihypertensive effect of the combination of amlodipine+olmesartan medoxomil was generally greater than the constituent amlodipine or olmesartan medoxomil monotherapies, regardless of subgroup. In general, more patients receiving combination therapy achieved BP goal than those treated with monotherapies. The safety and tolerability of combinations were similar to monotherapies across the subgroups. These results suggest that the combination of amlodipine+olmesartan medoxomil provides a safe and effective option for the treatment of hypertension in challenging patient populations.