We studied the effect of trandolapril 2 mg once-daily on mild-to-moderate essential hypertension in 325 overweight patients in an open-label, prospective, multicenter study. The male patients had a body mass index >25.5 kg/m(2), and the females >24 kg/m(2). Mild-to-moderate hypertension was defined as a baseline diastolic blood pressure (DBP) of 90 to 110 mm Hg. After a washout period of 2 weeks, patients were treated for 4 weeks. Efficacy analysis was performed on 295 patients. Mean systolic blood pressure (SEP) and DBP fell significantly from 155.7 +/- 16.7/95.8 +/- 8.8 mm Hg to 136.8 +/- 15.9/82.9 +/- 8.0 mm Hg at the end of treatment. The mean reductions in SEP and DBP were 20 mm Hg and 13 mm Hg, respectively. The target blood pressure (DBP <90 mm Hg and a reduction of at least 5 mm Hg) was achieved in 254 (86%) of 295 patients. There was a slight, statistically significant reduction in heart rate after drug therapy. Serum total cholesterol concentrations fell significantly from 216.5 +/- 40.5 mg/dL to 213.7 +/- 40.2 mg/dL, and low-density-lipoprotein cholesterol from 141.7 +/- 39.9 mg/dL to 138.3 +/- 39.4 mg/dL at the end of the trial. No other clinically important changes in hematologic or biochemical variables of clinical importance occurred. The overall incidence of adverse events was 9.6% and included headache in 9 patients, cough in 7, and dizziness in 6. Four patients (1.3%) withdrew from the study because of side effects, but the effects were transient and did not require treatment. We conclude that trandolapril is effective and safe for overweight patients with mild-to-moderate essential hypertension.