OBJECTIVE The objective of the study was to compare the effects of two different combined oral contraceptives on levels of plasma lipoproteins and coagulation factor VII. STUDY DESIGN A prospective randomized crossover study was undertaken. Thirty-five women were treated with combined oral contraceptives containing the same amount of ethinyl estradiol and either levonorgestrel or desogestrel. Levels of plasma lipoproteins and factor VII were determined before and after 2 months of treatment with each preparation. RESULTS Levels of high-density lipoprotein cholesterol were increased significantly with treatment with ethinyl estradiol/desogestrel when compared with baseline and treatment with ethinyl estradiol/levonorgestrel. A significant rise in plasma triglyceride levels was obtained with both preparations, although the increase was more pronounced with ethinyl estradiol/desogestrel. Plasma concentrations of factor VII mass concentration and activated factor VII were increased significantly only with ethinyl estradiol/desogestrel. CONCLUSION The rise in concentrations of high-density lipoprotein cholesterol may be advantageous, whereas the combined elevations of plasma triglyceride and factor VII levels obtained with ethinyl estradiol/desogestrel may reflect a hypercoagulable state.