To test whether a commercial weight loss program promotes greater weight loss in overweight or obese women compared with control conditions and to describe the effect on plasma lipids, carotenoids, hormones, and fitness. Overweight or obese women were randomized to commercial weight loss program or control conditions (n=35 each). At randomization, participants were 41.1 (11.4) (mean [standard deviation]) years, BMI 34.0 (3.5) kg/m2, and weight 92.0 (11.1) kg. At 6 months, change in weight by intent-to-treat (ITT) analysis was -7.2 (6.7) kg and -7.8% (7.2%) in the intervention group vs. -0.3 (3.9) kg and -0.3% (4.5%) in the control group (n=35 for each; p<0.01). One-year ITT analysis revealed significantly greater change in weight, percent weight, BMI, and waist and hip circumferences in the intervention vs. control group. Completers at 1 year exhibited change in weight of -7.3 (10.4) kg for the intervention group (n=32) vs. -0.7 (5.6) kg for controls (n=33) (p<0.01), and -7.8% (11.1%) weight change for the intervention group vs. -0.7% (6.2%) for controls (p<0.01). High-density lipoprotein (HDL) cholesterol concentration increased significantly in the intervention group. Fasting serum insulin decreased in the intervention but increased in the control group at 6 months (p<0.01), remaining different at 1 year (p=0.05). The commercial program successfully facilitated weight loss, which was notably maintained at 1 year, and promoted favorable changes in plasma lipid and hormone concentrations.