OBJECTIVE: Understanding the mechanisms of action of psychological treatments is a key first step in refining and developing more effective treatments. The present study examined hypothesized mediators of change of enhanced cognitive behavior therapy (CBT-E) and interpersonal psychotherapy for eating disorders (IPT-ED). METHOD: A series of mediation studies were embedded in a randomized controlled trial (RCT) comparing 20 weeks of CBT-E and IPT-ED in a transdiagnostic, non-underweight sample of patients with eating disorders (N = 130) consecutively referred to the service. Three hypothesized mediators of change in CBT-E (regular eating, weighing frequency, and shape checking) and the key hypothesized mediator of IPT-ED (interpersonal problem severity) were studied. RESULTS: The data supported regular eating as being a mediator of the effect of CBT-E on binge-eating frequency. The findings were inconclusive regarding the role of the other putative mediators of the effects of CBT-E; and were similarly inconclusive for interpersonal problem severity as a mediator of the effect of IPT-ED. DISCUSSION: This research highlights the potential benefits of embedding mediation studies within RCTs to better understand how treatments work. The findings supported the role of regular eating in reducing patients' binge-eating frequency. Other key hypothesized mediators of CBT-E and IPT-ED were not supported, although the data were not inconsistent with them. Key methodological issues to address in future work include the need to capture both behavioral and cognitive processes of change in CBT-E, and identifying key time points for change in IPT-ED.