Psychosocial risk factors cluster together, but generally a single factor approach has been adopted when studying their influence on health outcomes in cardiac patients. We examined the impact of clustering (i.e. type D personality and anxiety) on depressive symptoms 12 months post percutaneous coronary intervention (PCI). Prospective study. Consecutive patients (n=416), treated with PCI with drug-eluting stents, completed the type D Scale and the Hospital Anxiety and Depression Scale anxiety subscale at baseline, and the depression subscale at 12 months. Of all patients, 27% experienced depressive symptoms at 12 months. Depressive symptoms could not be attributed to cardiac events occurring during follow-up (P=0.76). The prevalence of depressive symptoms at 12 months was highest in patients with clustering (64%), followed by the single risk factors type D (45%) and anxiety (38%), with the lowest prevalence in the no risk factor group (neither anxiety nor type D) (13%; P<0.001). The single risk factors type D personality [odds ratio (OR): 5.82; 95% confidence interval (CI): 2.93-11.56] and anxiety (OR: 4.36; 95% CI: 2.23-8.55) and their co-occurrence (OR: 12.38; 95% CI: 6.11-25.09) remained independent significant predictors of depressive symptoms at 12 months compared with the no risk factor group, adjusting for baseline characteristics. Patients with the co-occurrence of type D personality and anxiety, two risk factors independently associated with adverse prognosis, had a considerably higher risk of depressive symptoms 12 months post PCI compared with patients with no or one risk factor. Further research is warranted to examine whether clustering of psychosocial risk factors also has deleterious effects on prognosis.