Appropriate control of blood pressure has been shown to reduce morbidity and mortality in patients with hypertension. Losartan potassium, a selective antagonist of the angiotensin II type 1 (AT1) receptor, has been shown to lower blood pressure in patients with hypertension. The purpose of this study was to compare the efficacy and tolerability of losartan and extended-release (ER) felodipine in Taiwanese patients with mild to moderate hypertension. Patients with mild to moderate hypertension (sitting diastolic blood pressure, 95-115 mm Hg) were enrolled in this prospective, randomized, parallel study. Sitting blood pressure, heart rate, adverse reactions, and serum biochemistry values were assessed during 2 weeks of placebo and 12 weeks of active treatment. Each patient received 50 mg of losartan or 5 mg of felodipine ER once daily, and the dosage was adjusted to double the initial level at week 6 if necessary. Of the 44 patients randomly allocated to receive losartan (n = 23) or felodipine (n = 21) therapy, 37 completed the study; three patients in the losartan group and four in the felodipine group withdrew because of adverse experiences, or were lost to follow-up. The mean reductions in sitting diastolic blood pressure at 6 and 12 weeks were significant with both losartan (-8.6 and -11.38 mm Hg, respectively) and felodipine (-9.2 and -10.69 mm Hg, respectively), and did not differ significantly between the two groups. Both losartan and ER felodipine were well tolerated by patients. However, the ER felodipine group had a significantly higher rate of drug-related flushing than the losartan group (24% vs 0%, p = 0.022). The results indicate that once-daily administration of losartan is as effective and well tolerated as once-daily ER felodipine in blood pressure reduction.