This study's purpose was to identify psychosocial predictors of weight loss maintenance in a multi-site clinical trial, following a group-based weight loss program. Participants (N = 1025) were predominately women (63%) and 38% were Black (mean age = 55.6 years; SD = 8.7). At 12 months, higher SF-36 mental health composite scores were associated with less weight regain (p < .01). For Black participants, an interaction existed between race and friends' encouragement for exercise, where higher exercise encouragement was related to more weight regain (p < .05). At 30 months, friends' encouragement for healthy eating was associated with more weight regain (p < .05), whereas higher SF-36 mental health composite scores were related to less weight regain (p < .0001). Perceived stress and select health-related quality of life indices were associated with weight regain; this relationship varied across gender, race, and treatment conditions. Temporal changes in these variables should be investigated for their impact on weight maintenance.