Depressive symptoms are highly relevant in patients with (CAD). Unfortunately, recent psychotherapy trials showed only small effects on depression. However, combined treatment may be more efficacious than a behavioural or interpersonal treatment alone. In our new multicenter trial, funded by the German Research Foundation, we address negative affectivity and social inhibition in addition to depression to enhance treatment efficacy. Men and women (n=569, age 18-75 y) with HADS depression scores >7 hospitalized for any manifestation of CAD, are randomized into the intervention or control group. Initially, patients in intervention receive 3 sessions of supportive individual psychotherapy on a weekly basis. After reevaluation of depression 4 weeks after inclusion, patients with persisting symptoms of depression receive 25 sessions of combined psychodynamic and group cognitive behavior therapy (CBT) over 10 months. The control group receives one counselling session. Routine cardiac care is offered to both groups. Primary efficacy endpoint is change from baseline to year 1 in HADS depressive symptoms. Secondary endpoints include remission of depression, Type D pattern, health-related quality of life, cardiovascular risk profile, neuroendocrine and inflammatory activation, heart rate variability, cardiac events, and health care utilization, up to 24 months after inclusion. Preplanned subgroup analyses will assess gender, and genetic predictors of treatment success. Psychosomatic Clinic, U Medicine, Mainz, Germany; 2 Psychosomatics, U Clinic Cologne, Cologne, Germany; 3 Psychosomatics, U Medical Center, Berlin, Germany; 4 Psychosomatics, U Clinic Freiburg, Freiburg, Germany; 5 Psychosomatics, Medical School, Hannover, Germany; 6 Psychosomatics, U Clinic Dresden, Dresden, Germany; 7 Psychocardiology, Kerckhoff Reha Center, Bad Nauheim, Germany; 8 Gen. Internal and Psychosomatic Med, U Clinic Heidelberg, Heidelberg, Germany; 9 Psychosomatics, TU Munich, Munich, Germany; 10 Psychosomatics, U Clinic Dresden, Dresden, Germany; 11 Psychosomatics, Klinikum Nord Nürnberg, Nürnberg, Germany and 12 Psychosomatics, U Clinic Göttingen on behalf of SPIRR-CAD Study Group, Göttingen, Germany.