The present study was designed to compare the safety and efficacy of the new angiotensin-converting enzyme inhibitor moexipril with that of hydrochlorothiazide (HCTZ) in postmenopausal women with mild-to-moderate hypertension. After a 4-week single-blind placebo period, 97 postmenopausal hypertensive women (42–74 years of age) with a sitting diastolic blood pressure (SDBP) of 95–114 mm Hg were randomized to receive either once daily moexipril 15 mg or HCTZ 25 mg for a 12-week double-blind treatment period. At study endpoint, HCTZ caused significantly greater increases from baseline in serum uric acid levels than did moexipril (0.8 ± 0.1 vs. 0.1 ± 0.1 mg/dl, p < 0.01). Furthermore, 12-week treatment with HCTZ resulted in significant increases in glucose (+11.0 ± 4.1 mg/dl) and total cholesterol/HDL ratio (+0.3±0.1 mg/dl) and a significant decrease in HDL (–3.2±0.7 mg/dl). In contrast, moexipril treatment was not associated with significant changes in any metabolic parameter. Both drugs efficiently lowered SDBP with reductions of –10.0 ± 1.3 and –11.8 ± 1.1 mm Hg in the moexipril and HCTZ group, respectively. Clinical adverse events were reported by a greater percentage of HCTZ patients (53%) than moexipril patients (40%), with headache and rhinitis as the most frequent events. The results indicate that moexipril was better tolerated than HCTZ in postmenopausal women and did not adversely affect metabolic parameters. Both drugs were effective in lowering blood pressure.