OBJECTIVE: To examine the cost-effectiveness of sibutramine plus a structured weight management program (WMP) versus only structured WMP. METHODS: Cost-effectiveness analysis based on a randomized controlled trial conducted within a managed care organization. The target population was obese or overweight persons. The economic time horizon was two years (pre and post study enrollment). Perspective was from that of a managed care organization. The treatment arms consisted of either sibutramine plus structured WMP or only WMP. The primary outcomes were change in weight and percent change in weight over 12 months, and change in obesity-related and total medical costs 12 months prior to and 12 months after enrollment. Non-parametric bootstrap was used to generate 95% confidence intervals for incremental cost-effectiveness ratios. RESULTS: A total of 501 subjects were enrolled in the study, 281 receiving sibutramine plus structured WMP and 220 receiving only structured WMP. The mean (SD) weight loss was significantly greater in the sibutramine (13.7 (15.5) lbs) group than the non-drug group (5.0 (13.2) lbs) (p<0.001). Obesity-related total cost between groups were different (p<0.001), with a median of $408 for sibutramine compared to $58 for the non-drug group. The ICER for sibutramine was $44 (95% CI: $42 to $46) per additional pound of weight loss. Sensitivity analysis suggested that changes in physician costs a negligible effect on the results. If the cost of sibutramine was excluded, there was no difference between the groups with respect to obesity-related costs. A limitation of this study is that costs were estimated using national fees schedules for hospital and physician visits and average wholesale price for medications. CONCLUSION: Patients enrolled in a weight management program receiving sibutramine had greater weight loss and decrease in BMI at greater cost than did patients enrolled in the same program who did not receive sibutramine.