Objective To determine whether older primary care patients with a Major Depressive Disorder (MDD) have lower heart rate variability (HRV) compared to non-depressed patients. HRV is a measure of cardiac autonomic functioning. Method A cross-sectional comparison of 136 elderly persons with MDD and 136 non-depressed controls (matched forage and gender) recruited in family practices in the Netherlands. Depression was determined according to the DSM-IV criteria using the PRIME-MD. HRV was measured with an electrocardiogram (ECG) during a 5-minute supine rest. Results Multivariate analyses showed statistically significant decrease in HRV in MDD patients compared with controls. Conclusion Older primary care patients with MDD have a reduced HRV. This may explain why depression is a risk factor for cardiovascular disease and mortality.