BACKGROUND We sought to identify factors associated with participant retention in a 2-year, physician-lead, multidisciplinary, clinical weight management program that employs meal replacements to produce weight loss and intensive behavioral interventions and financial incentives for weight loss maintenance. We studied 270 participants enrolled in 2010 and 2011. Sociodemographic factors, health insurance, distance traveled, body mass index, comorbidities, health-related quality-of-life, and depression were explored as potential predictors of retention. RESULTS Mean age was 49 ± 8 years and BMI was 41 ± 5 kg/m(2). Retention was excellent at 3 months (90%) and 6 months (83%). Attrition was greatest after participants were transitioned to regular foodstuffs and fell to 67% at 12 months and 51% at 2 years. Weight decreased by 15 ± 12 kg and BMI decreased by 5.1 ± 4.0 kg/m(2) in 2-year completers. Older age, lower baseline BMI, and financial incentives for program participation were independently associated with retention. Fewer depressive symptoms at baseline were associated with retention. CONCLUSIONS This multidisciplinary, clinical, weight management program demonstrated high retention and excellent outcomes. Older age at baseline, less extreme obesity, and financial incentives were associated with program retention.