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OBJECTIVE Test the hypothesis that the efficacy of a dissonance-based obesity/eating disorder prevention program, Project Health, could be enhanced by implementing it in single-sex groups and adding food response inhibition and attention training. METHOD Using a 2 × 2 factorial design, young adults (N = 261; Mage = 19.3, 79% female; 64% White) were randomized to (a) single-sex or (b) mixed-sex groups that completed food response inhibition and attention training or (c) single-sex or (d) mixed-sex groups that completed generic response inhibition and attention training with nonfood images. Preregistered primary outcomes (body fat, Body Mass Index [BMI]), eating disorder symptoms and other outcomes were assessed at pretest and posttest. RESULTS For one preregistered primary outcome, body fat loss, there was a significant interaction between the two manipulated factors (d = -.28), as well as significant main effects for sex composition of groups (d = -.18) and food response inhibition and attention training (d = -0.17), with the largest body fat loss occurring for single-sex groups implemented with food response inhibition and attention training. Although the two manipulated factors did not significantly affect the other outcomes (including BMI, the other preregistered primary outcome), there was a significant reduction in eating disorder symptoms across the conditions (within participant d = -.78), converging with prior evidence that Project Health produced larger reductions in symptoms than educational control participants. CONCLUSIONS Results suggest that implementing Project Health in single-sex groups with food response inhibition and attention training produced the largest body fat loss effects, as well as significant reductions in eating disorder symptoms, suggesting that efforts to disseminate this prevention program are warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved).