Background: Depression affects 20% of people with coronary heart disease (CHD) and predicts worse health-related quality of life (HRQoL), but in primary studies the strength of this reported relationship has been inconsistent. Aims and methods: We conducted a systematic review to investigate the extent to which depression independently predicts subsequent physical HRQoL. We searched electronic databases (MEDLINE, PsycINFO, CINAHL and EMBASE) to identify prospective cohort studies that included CHD patients, focused on depression and subsequent physical HRQoL using standardised measures. Included studies were assessed for methodological quality. Results: We identified 11 independent studies, of which nine showed a significant association between depression and subsequent physical HRQoL. There was no systematic methodological difference between those studies that did and did not show a significant association; in particular the results did not appear to be affected by the way depression or physical HRQoL was measured. Five of the 11 studies were of moderate to high methodological quality and controlled for both HRQoL and the severity of CHD at baseline. Four studies showed a significant association between depression and HRQoL. Conclusions: Depression predicts subsequent physical HRQoL and this association was not attributable to confounding effects of baseline HRQoL or the severity of the CHD. Identification of depressed CHD patients may improve targeting of resources at people at increased risk of worse physical HRQoL. Treating depression may improve subsequent physical HRQoL, though this needs to be established in future randomised controlled trials. © The European Society of Cardiology 2012.