PURPOSE: To evaluate the long-term impact of Medifast meal-replacement supplements (MMRS) combined with appetite suppressant medication (ASM) among participants who received 52 weeks of treatment. METHODS: We conducted a systematic program evaluation of weight loss data from a medically-supervised weight control program combining the use of MMRS and ASM. Data were obtained and analyzed from 1,351 patient (BMI> or =25) medical charts who had participated for at least 12 weeks of treatment. Outcomes included weight loss (kg) and percent weight loss from baseline and at 12, 24, and 52 weeks. Both completers and intention-to-treat analyses were conducted. Completers' (i.e., those with complete data for 52 weeks) outcomes were evaluated after stratification for reported adherence to the MMRS and ASM. RESULTS: Participants who completed 52 weeks of treatment experienced substantial weight losses at 12 (-9.4+/-5.7 kg), 24 (-12.0+/-8.1 kg), and 52 weeks (-12.4+/-9.2 kg) and all measures were significantly different from baseline weight (p<0.001 for all contrasts) for both true completers (n=324) and for ITT analysis (n=1,351). Fifty percent of patients remained in the program at 24 weeks and nearly 25% were still participating at one year. CONCLUSIONS: This weight loss program using a combination of MMRS and ASM produced significant and sustained weight losses at 52 weeks. Results were better than those typically reported for obesity pharmacotherapy in both short- and long-term studies and also better than those reported for partial meal replacement programs. Program retention at one year was similar to that reported in many controlled drug trials and better than most commercial programs reported in the literature.