Objective: To evaluate the effect of three different dosages of transdermally administered 17β-estradiol on serum lipoproteins in women who had recently experienced surgical menopause. Material and Methods: We undertook a 2-year, randomized, double-blind, placebo-controlled study in which 126 subjects were recruited and stratified by age, and 93 patients completed the protocol. Serum lipoproteins were assessed before initiation of treatment and after 12 and 24 months of therapy with 0.025, 0.05, or 0.1 mg of estradiol daily. Results: Total serum cholesterol and low-density lipoprotein cholesterol showed dose-dependent decreases that reached statistical significance after 2 years of treatment with transdermally administered estradiol. Conclusion: This study confirms that transdermally administered 17β-estradiol has a modest beneficial effect on serum lipoproteins, with decreased levels of total cholesterol and low-density lipoprotein cholesterol.