Alterations in plasma cholesterol concentrations, especially increases in low-density lipoprotein (LDL), are well-known risk factors in the development of atherosclerosis. Numerous studies have examined the lipid-lowering effects of functional soy-containing foods, but few have specifically examined soymilk, with equivocal findings reported. In September 2008, a single-blind, randomized, controlled trial was conducted on 32 postmenopausal women at Baylor University, Waco, TX, USA. After a 2-week run-in period, subjects were randomly assigned to consume three servings of vanilla soy (n=16) or reduced-fat dairy (n=16) milk per day for 4 weeks. Plasma lipid profiles were obtained pre- and post-supplementation. Plasma high-density lipoprotein, LDL, and triglycerides were not significantly different between groups post-intervention (P=.45) or from baseline (P=.83). Separate analysis of plasma total cholesterol levels yielded similar results (P=.19 and P=.92, respectively). Furthermore, subanalyses controlling for dyslipidemia (n=23) and lipid-lowering medication usage (n=28) did not significantly alter results. Despite good dietary compliance, our study failed to show a significant hypocholesterolemic effect of soymilk consumption in this postmenopausal female population. Potential reasons for this nonsignificant finding are discussed, and future research directions are presented.