Objectives: Determine whether self-efficacy independently predicted weight loss in a behavioral intervention and explore factors that influence the path between self-efficacy and weight change. Design: Secondary analysis of the PREMIER trial, a randomized controlled trial testing effects of lifestyle interventions on blood pressure. Setting: Four academic medical centers. Participants: PREMIER recruited adults (n = 810) with pre-hypertension/stage 1 hypertension, not currently receiving medication. This analysis excluded participants in the control arm, resulting in n =537. Interventions: Participants were randomly assigned to 1 of 3 groups: advice only, established lifestylerecommendations, or established lifestyle recommendations plus Dietary Approaches to Stop Hypertension dietary pattern. Main Outcome Measures: Self-efficacy (dietary self-efficacy [DSE], exercise self-efficacy [ESE]), dietary intake, fitness. Analysis: Pearson correlations, 1-way analysis of variance, mediation analyses. Results: Despite an overall decrease in DSE/ESE, change in DSE/ESE significantly predicted weight change at 6 (β = -21, P < .01; β = -19, P < .01, respectively) and 18 months (β = -19, P < .01; β=-35, P < .01). Change in percent calories from fat partially mediated the DSE/weight change relationship at 6 months. Change in fitness partially mediated the ESE/weight change relationship at 18 months. Conclusions and Implications: Changes in DSE/ESE were not associated with behavior change as hypothesized. Additional research is needed to identify mediators between self-efficacy and adoption of behaviors that influence weight loss. © 2013 Society for Nutrition Education and Behavior.