OBJECTIVE: The objective of this study was to compare the effects on serum lipid levels and oxidation of non-high density lipoprotein (HDL) fraction of tibolone with that of transdermal estrogen. STUDY DESIGN: The study included thirty women in total (fifteen in each treatment group) between 44 and 58 years of age. Serum concentrations of lipids and apolipoproteins, lipoprotein (a), total carotene, vitamin E and various water-soluble antioxidants were measured. We analyzed the susceptibility of non-HDL fraction to copper-mediated oxidation. RESULTS: Tibolone users had lower triglyceride (TG), HDL-cholesterol (HDL-C) and very low density lipoprotein-cholesterol and higher carotene/TG, vitamin E/TG and vitamin E/total cholesterol+TG levels. The amount of malondialdehyde (measured as thiobarbituric acid-reactive substances) generated during oxidation was significantly lower in the tibolone-receiving group at the 120th, 150th and 180th minutes of incubation. CONCLUSION: Our study indicates that tibolone protects apolipoprotein B-containing lipoproteins in postmenopausal women from oxidation that is related to its effects on serum lipid concentrations.