Objective: Both Mindfulness Based Cognitive Therapy (MBCT) and Cognitive Therapy (CT) enhance self-management of prodromal symptoms associated with depressive relapse, albeit through divergent therapeutic procedures. We evaluated rates of relapse in remitted depressed patients receiving MBCT and CT. Decentering and dysfunctional attitudes were assessed as treatment-specific process markers. Method: Participants in remission from Major Depressive Disorder (MDD; N = 166) were randomized to 8 weeks of either MBCT (N = 82) or CT (N = 84) and were followed for 24 months, with process markers measured every 3 months. Attendance in both treatments was high (6.3/8 session) and treatment fidelity and competence were evaluated. Relapse was defined as a return of symptoms meeting the criteria for major depression on Module A of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID). Results: Intention-to-treat analyses indicated no differences between MBCT and CT in either rates of relapse to MDD or time to relapse across 24 months of follow up. Both groups experienced significant increases in decentering and participants in CT reported greater reductions in dysfunctional attitudes. Within both treatments, participants who relapsed evidenced lower decentering scores than those who stayed well over the follow up. Conclusions: This is the first study to directly compare relapse prophylaxis following MBCT and CT directly. The lack of group differences in time to relapse supports the view that both interventions are equally effective and that increases in decentering achieved via either treatment are associated with greater protection. These findings lend credence to Teasdale et al.’s (2002) contention that, even though they may be taught through dissimilar methods, CT and MBCT help participants develop similar metacognitive skills for the regulation of distressing thoughts and emotions.