With negative treatment trials, the role of depression as an aetiological or prognostic factor in coronary heart disease (CHD) remains controversial. We quantified the effect of depression on CHD, assessing the extent of confounding by coronary risk factors and disease severity. Meta-analysis of cohort studies measuring depression with follow-up for fatal CHD/incident myocardial infarction (aetiological) or all-cause mortality/fatal CHD (prognostic). We searched MEDLINE and Science Citation Index until December 2003. In 21 aetiological studies, the pooled relative risk of future CHD associated with depression was 1.81 (95% CI 1.53-2.15). Adjusted results were included for 11 studies, with adjustment reducing the crude effect marginally from 2.08 (1.69-2.55) to 1.90 (1.49-2.42). In 34 prognostic studies, the pooled relative risk was 1.80 (1.50-2.15). Results adjusted for left ventricular function result were available in only eight studies; and this attenuated the relative risk from 2.18 to 1.53 (1.11-2.10), a 48% reduction. Both aetiological and prognostic studies without adjusted results had lower unadjusted effect sizes than studies from which adjusted results were included (P<0.01). Depression has yet to be established as an independent risk factor for CHD because of incomplete and biased availability of adjustment for conventional risk factors and severity of coronary disease.