BACKGROUND Depression is a debilitating mental health problem that tends to run a chronic, recurrent course. Even when effectively treated, relapse and recurrence rates remain high. Accordingly, interventions need to focus not only on symptom reduction, but also on reducing the risk of relapse by targeting depression-related disturbances that persist into remission. We are addressing this need by investigating the efficacy, acceptability and feasibility of a MEmory Specificity Training (MEST) programme, which directly targets an enduring cognitive marker of depression - reduced autobiographical memory specificity. Promising pilot data suggest that training memory specificity ameliorates this disturbance and reduces depressive symptoms. A larger, controlled trial is now needed to examine the efficacy of MEST. This trial compares MEST to an education and support (ES) group, with an embedded mechanism study. METHODS/DESIGN In a single blind, parallel cluster randomised controlled trial, 60 depressed individuals meeting diagnostic criteria for a current major depressive episode will be recruited from the community and clinical services. Using a block randomisation procedure, groups of 5 to 8 participants will receive five weekly sessions of MEST (n = 30) or education and support (n = 30). Participants will be assessed immediately post-treatment, and at 3- and 6-months post-treatment (MEST group only for 6-month follow-up). Depressive symptoms at 3-month follow-up will be the primary outcome. Secondary outcomes will be change in depressive status and memory specificity at post-treatment and 3-months. The 6-month follow-up of the MEST group will allow us to examine whether treatment gains are maintained. An explanatory question will examine variables mediating improvement in depression symptoms post-treatment and at 3-month follow-up. DISCUSSION This trial will allow us to investigate the efficacy of MEST, whether treatment gains are maintained, and the mechanisms of change. Evidence will be gathered regarding whether this treatment is feasible and acceptable as a low-intensity intervention. If efficacy can be demonstrated, the results will support MEST as a treatment for depression and provide the foundation for a definitive trial. TRIAL REGISTRATION NCT01882452 (ClinicalTrials.gov), registered on 18 June 2013.