Objective: To implement a randomized trial to evaluate the effectiveness of a weight loss program delivered using synchronous distance education compared with a wait-list control group with 6-month follow-up. Methods: Adults with a body mass index (BMI) 25 were randomized to the intervention (n 5 42) or waitlist control group (n 5 38). The intervention group participated in a synchronous, online, 15-week weight loss program; weight loss was the primary outcome. Secondary measures included height, BMI, and confidence in ability to be physically active and eat healthy. Assessments occurred at three and four time points in the intervention and control group, respectively. Results: Participants who completed the program lost significantly more weight (1.8 kg) than those in the wait-list control group (0.25 kg) at week 15 [F(1,61) 5 6.19, P 5 0.02] and had a greater reduction in BMI (0.71 vs. 0.14 kg/m 2 ), [F(1,61) 5 7.45, P 5 0.01]. There were no significant differences between the intervention and the wait-list control groups for change in confidence in ability to be physically active or eat healthy. Weight loss was maintained at 6 months. Conclusions: Use of synchronous distance education is a promising approach for weight loss. The results of this study will help to inform future research that employs Web-based interventions.