We tested the hypothesis that a 2-month intervention with unopposed oral conjugated equine estrogens (0.625 mg/d) would decrease lipid oxidation, as assessed by 24-hour, whole-room, indirect calorimetry in 14 postmenopausal women. Estrogen (E) treatment was associated with declines in both 24-hour and postprandial lipid oxidation and an increase in fat mass (mean [±SD] 2-month difference 1.1 ± 1.0 kg; mean 6-month difference 1.8 ± 2.2 kg), suggesting that, on an acute basis, oral E may increase adiposity by limiting lipid oxidation. © 2008 American Society for Reproductive Medicine.