on behalf of the MAPPY Study InvestigatorsThe treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/ hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n¼109) or a high-dose therapy with 100 mg losartan (n¼107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3 ± 10.1 to 131.5 ± 11.5 mm Hg by combination therapy (Po0.001) and from 151.0 ± 9.3 to 142.5 ± 13.6 mm Hg by high-dose therapy (Po0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (Po0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (Po0.001), and high-dose therapy decreased evening SBP from 138.9 ± 9.9 to 131.4 ± 13.2 mm Hg (Po0.01). Although both therapies improved target BP achievement rates in the morning and evening (Po0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (Po0.001 and Po0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (Po0.001 and Po0.01, respectively). Combination therapy decreased urine albumin excretion (Po0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (Po0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.