Depression and sub-syndromal depressive symptoms are important predictors of morbidity and mortality after acute coronary syndrome (ACS). Prior trials of depression treatment in post-ACS patients have demonstrated no improvement for event-free survival, and only modest improvement in depression symptoms. These trials have raised a number of important issues regarding timing of depression intervention, acceptability of depression treatment to ACS patients, and safety for subsets of the treated population. This article describes Project COPES (Coronary Psychosocial Evaluation Studies), a multi-center Phase-I randomized clinical trial. Project COPES uses a patient preference depression treatment that has previously been found acceptable to medical patients, and a 3-month pre-randomization observation period to insure depression status. The study sample will include 200 post-ACS patients. The primary outcome is patient satisfaction with depression care. Secondary, exploratory aims include the acceptability of depression treatment, reduction in depressive symptoms, and the effects of treatment on two key pathways--medication adherence and inflammation--hypothesized to link depression to post-ACS prognosis. These analyses will provide important data to inform subsequent clinical trials with this population.