Objective— To compare the metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. Research Design and Methods— After a 2-wk run-in period on dietary treatment alone, 12 Chinese normotensive patients with uncomplicated NIDDM were randomized to receive either metformin, or glibenclamide for 4 wk before being crossed-over to the alternative treatment for an additional 4 wk. Metabolic and hemodynamic index, including cardiac output estimation by impedance cardiography, were measured at baseline and at the end of each treatment period. Results— Body mass index was reduced more with metformin than with glibenclamide, although glycemic control was similar with both drugs. Plasma total cholesterol concentration fell more with metformin (mean difference −0.65 mM, 95% confidence interval −0.96 to −0.32) than glibenclamide (mean difference −0.20 mM, 95% confidence interval −0.54–0.12) (P < 0.05). Compared with baseline values, erect diastolic blood pressure was reduced more by metformin (12.9% [95% confidence interval −21.5 to −4.4%]) than glibenclamide (−6.8% [95% confidence interval −14.9 to 1.2%]) (P < 0.001). The relative changes in the systemic vascular resistance index also differed between the two treatments (glibenclamide, 6.2 [−4.3 to 16.6%]; metformin, −1.2 [95% confidence interval −8.8−6.4%]) (P < 0.05)]. Conclusions— In normotensive NIDDM patients, treatment with metformin was associated with greater reductions in body weight, plasma total cholesterol concentration, and erect diastolic blood pressure, whereas the systemic vascular resistance index increased after treatment with glibenclamide. These findings merit long-term investigation.