BACKGROUND: Losartan, the first of the angiotensin II receptor blockers (ARBs) to be introduced, has been studied extensively in comparison with other classes of antihypertensive agents. Less research has been conducted on the efficacy and tolerability of losartan compared with that of other ARBs. OBJECTIVE: This randomized, multicenter, double-blind, parallel-group equivalence study was conducted to compare the antihypertensive efficacy and tolerability of a once-daily regimen of losartan with that of valsartan. METHODS: Patients > or = 21 years of age with mild to moderate hypertension, defined as a trough sitting diastolic blood pressure (SiDBP) between 95 and 115 mm Hg, were randomized to receive once-daily losartan (50 mg) or valsartan (80 mg) for 12 weeks. At the end of the sixth treatment week, patients in both groups with trough SiDBP > or = 90 mm Hg had their dose doubled for the remainder of the treatment period. Analysis of variance was used to compare treatment groups with respect to change in mean trough SiDBP from baseline to week 12. Within-treatment changes were analyzed using the paired t test. With at least 220 patients per treatment group, the study had 90% power to place a 90% CI on the difference between losartan and valsartan in SiDBP within the equivalence interval of +/- 2.5 mm Hg. RESULTS: A total of 495 patients were randomized, 247 to the losartan group and 248 to the valsartan group: 456 patients completed the study. Adjusted mean change from baseline values for trough SiDBP atthe end of 12 weeks of treatment were significantly different (P < 0.001) from zero in both the losartan group (-9.9 mm Hg) and the valsartan group (-10.1 mm Hg). At week 12, losartan was as effective as valsartan in lowering SiDBP, with a between-group difference of 0.2 mm Hg (90% CI, -1.3 to 1.7; P = 0.827). At week 6, the difference in SiDBP between groups was -1.3 mm Hg (90% CI, -2.7 to 0.0; P = 0.106). A similar pattern of results was obtained at weeks 6 and 12 for sitting systolic blood pressure. The percentage of patients reaching the SiDBP goal at week 6 (46% [112/2411 losartan; 42% [103/245] valsartan) and week 12 (57% [139/243] losartan; 59% [145/245] valsartan) was not significantly different between the treatment groups. Both losartan and valsartan were similarly well tolerated. Over the 12 weeks, the laboratory profiles of the 2 drugs were similar except for serum uric acid levels, which decreased from 6.0 to 5.7 mg/dL in the losartan group and increased from 5.9 to 6.0 mg/dL in the valsartan group (P = 0.001 for between-treatment difference). CONCLUSIONS: At starting and titrated doses, losartan and valsartan are similarly effective in reducing blood pressure in patients with mild to moderate hypertension. Losartan, but not valsartan, was associated with a decrease in serum uric acid levels.