The present study tested hypothesized mechanisms underlying the effects of two selective prevention interventions targeting both obesity and eating disorders (Healthy Weight and the newly developed Project Health), relative to video control. Tests examined mediation for the significant weight gain prevention and eating disorder symptom prevention effects previously reported. College students (N = 364; 72% women) with weight concerns were randomized to condition and assessed for 2-years post-intervention. Project Health participants had significant improvements in 2 of the 7 proposed mediators relative to comparisons (i.e., cognitive dissonance, the unhealthy Western dietary pattern) but change in these variables did not mediate its effect on long-term BMI change. Two variables emerged as full mediators of the eating disorder prevention effects for both experimental interventions - body dissatisfaction and negative affect. Analyses failed to support the exploratory hypothesis that change in eating disorder symptoms mediated the effects of condition on BMI gain. This report is the among the first to examine mediation for programs aimed at preventing both weight gain and eating disorders, particularly in mixed-gender groups. Mediational analyses are essential in identifying the mechanism of intervention action, which can inform improvements to prevention programs.