OBJECTIVE: Depression is associated with an increased risk of cardiac morbidity and mortality in patients following myocardial infarction (MI). Our objective was to investigate the potential role of the autonomic nervous system in mediating this detrimental effect. METHODS: The study group consisted of 95 consecutive post-MI patients without depression and 53 post-MI patients with depression. Depressive symptoms were assessed by the Beck Depression Inventory (BDI). Activity of the autonomic nervous system was assessed by analysing heart rate variability (HRV) using 24-hour ambulatory electrocardiographic recordings as obtained three months post MI. RESULTS: Higher age, female gender and left ventricular ejection fraction <0.40 were associated with lower HRV (SDANN, and very-low-frequency and low-frequency power, but not RMSSD and high-frequency power), as was depression. In the multivariate analysis, age and left ventricular ejection fraction but not gender emerged to be independently associated with HRV. After adjustment for these two covariates, depression remained significantly associated with low HRV. CONCLUSIONS: Patients with depression in the present post-MI study are characterised by decreased longer-range HRV compared with the patients without depression, independent of other clinical variables. This observation supports the concept that one of the mechanisms underlying the detrimental effect of depression on post-MI prognosis may be that depression adds to the autonomic derangement post MI.