Few studies have examined predictors of weight regain after significant weight losses. This prospective study examined behavioral and psychological predictors of weight regain in 261 successful weight losers who completed an 18-month trial of weight regain prevention that compared a control condition with self-regulation interventions delivered face-to-face or via the Internet. Linear mixed effect models were used to examine behavioral and psychological predictors of weight regain, both as main effects and as interactions with treatment group. Decreases in physical activity were related to weight regain across all 3 groups, and increased frequency of self-weighing was equally protective in the 2 intervention groups but not in the control group. Increases in depressive symptoms, disinhibition, and hunger were also related to weight regain in all groups. Although the impact of changes in restraint was greatest in the Internet group and weakest in the face-to-face group, the latter was the only group with increases in restraint over time and consequent decreases in magnitude of weight regain. Future programs should focus on maintaining physical activity, dietary restraints, and frequent self-weighing and should include stronger components to modify psychological parameters.