The present study aimed to evaluate the effect of an oral contraception formulation with drospirenone (Yasmin((R))) on lipid metabolism. An open-label, non-comparative clinical trial was conducted. One hundred women, who desired oral contraception for at least 6 months, were recruited. The subjects received a blister pack which contained 21 tablets of 3 mg drospirenone/30 mu g ethinyl estradiol for the first four cycles (1 cycle =28 days). Cycle 5 and 6 blister packs were dispensed during the next visit in cycle 4. Serum from each subject was collected and analyzed for lipid profile levels at baseline and at cycle 6. The mean differences in lipid profile levels at cycle 6 compared with baseline were assessed. Of the total 100 subjects, 92 (92%) completed the study. There was no significant change in total cholesterol. At cycle 6, high-density lipoprotein cholesterol (HDL-C) and triglycerides increased significantly by 25.7% and 42.0%, respectively, compared with baseline. However, low-density lipoprotein cholesterol (LDL-C) decreased significantly by 9.9% at cycle 6 compared with baseline. Our results show that the new oral contraception formulation with drospirenone (Yasmin) is well tolerated and has good contraceptive efficacy. The observed favorable changes in HDL-C and LDL-C suggest a potential cardioprotective benefit.