BACKGROUND: Obesity-related comorbidities frequently contribute to acute illness. Obesity interventions during hospitalization are not often utilized but may be effective. OBJECTIVE: To examine whether inpatient weight loss intervention with postdischarge follow-up results in weight loss at 6 months when compared to control. DESIGN: Prospective, randomized controlled trial. SETTING: Academic medical center in Chicago, Illinois. PATIENTS: Obese adult inpatients. INTERVENTION: Intervention subjects viewed a weight education video, underwent personalized counseling, and set specific weight loss, dietary, and fitness goals prior to discharge. All participants were followed by phone over the subsequent 6 months. The trial was unblinded to participants, physicians, and investigators. MEASUREMENTS: Primary outcome was weight change between groups at 6 months. Weight change from baseline and waist-to-hip ratios (WHR) were also assessed. RESULTS: For 176 participants in the intention-to-treat analysis, mean baseline weight for the intervention group was 107.7 kg (standard deviation [SD]=16.7) and 105.1 kg (SD=17.4) for controls. Mean weight loss at 6 months was 1.08 kg (SD=4.33) for intervention subjects and 1.35 kg (SD=3.65) among controls. There was no significant difference in weight loss between groups at 6 months (P=0.26). As-treated analysis yielded similar results. There were no differences in WHRs between the intervention and control at 6 months (0.04 vs 0.04, P=0.59). CONCLUSIONS: We found no difference in weight loss between the intervention and control groups at 6 months.