Diltiazem increases systemic exposure to simvastatin via inhibition of CYP3A. This study assessed the impact of this interaction on the lipid-lowering effects of simvastatin. Chinese patients with hypercholesterolemia were randomized to receive simvastatin 20 mg daily alone or together with diltiazem 60 mg 3 times daily for 4 weeks with a washout period of 4 weeks in an open-label, crossover study. Blood pressure, fasting serum lipid profile, and safety tests were determined at baseline and after each treatment period. Trough serum diltiazem was measured at the end of the 4-week combination treatment. In the 30 patients who completed the study, simvastatin treatment significantly reduced low-density lipoprotein cholesterol by mean (± standard error) 41.0% ± 2.2% (P < .001), and the combination with diltiazem showed an additional reduction of 1.66% (95% confidence interval: -4.63 to 7.96, P > .05). The additional change in low-density lipoprotein cholesterol with diltiazem showed a nonsignificant positive correlation with the trough serum diltiazem concentration (R(2) = 0.142, P = .058). Co-administration of diltiazem 60 mg 3 times daily with simvastatin 20 mg daily tended to increase the changes in lipid parameters in these Chinese subjects, but the effects did not reach significance.