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 lifestyle recommendations, 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.