Context: Although commercial weight loss programs provide treatment to millions of clients, their efficacy has not been evaluated in rigorous long-term trials. Objective: To compare weight loss and health benefits achieved and maintained through self-help weight loss vs with a structured commercial program. Design and Setting: A 2-year, multicenter randomized clinical trial with clinic visits at 12, 26, 52, 78, and 104 weeks conducted at 6 academic research centers in the United States between January 1998 and January 2001. Participants: Overweight and obese men (n=65) and women (n=358) (body mass index, 27-40) aged 18 to 65 years. Intervention: Random assignment to either a self-help program (n =212) consisting of two 20-minute counseling sessions with a nutritionist and provision of self-help resources orto a commercial weight loss program (n=211) consisting of a food plan, an activity plan, and a cognitive restructuring behavior modification plan, delivered at weekly meetings. Main Outcome Measures: Weight W6ight change was the primary outcome measure. Secondary outcomes included waist circumference, body mass index, blood pressure, serum lipids, glucose, and insulin levels. Results: At 2 years, 150 participants (71%) in the commercial group and 159 (75%) in the self-help group completed the study. In the intent-to-treat analysis, mean (SD) weight loss of participants in the commercial group was greater than in the self-help group at 1 year (-4.3 [6.1] kg vs 1.3 [6.1] kg, respectively; P<.001) and at 2 years (-2.9 [6.5] kg vs -0.2 [6.5] kg, respectively; P<.001). Waist circumference (P=.003) and body mass index (P<.001) decreased more in the commercial group. Changes in blood pressure, lipids, glucose, and insulin levels were related to changes in weight in both groups, but between-group differences in biological parameters were mainly nonsignificant by year 2. Conclusion: The structured commercial weight loss program provided modest weight loss but more than self-help over a 2-year period.