Panic disorder (PD) and coronary artery disease (CAD) often co-occur, and CAD patients with comorbid PD suffer greater cardiovascular morbidity and mortality relative to CAD patients without PD. However, the mechanisms underlying these associations are still unknown. Reduced heart rate variability (HRV), a non-invasive measure of cardiac autonomic modulation, is an important predictor of adverse cardiac events. Interestingly, reduced HRV has been observed in patients with panic-like anxiety and PD, as well as in various CAD populations. However, the extent to which HRV is altered in patients with both PD and CAD is unknown. This study evaluated HRV in 42 CAD patients with (n=20) and without (n=22) PD. Patients underwent 48-h electrocardiographic monitoring. Power spectral analysis of HRV indicated that CAD patients with PD exhibited significantly lower LF/HF ratios, which may reflect lower sympathetic modulation, compared with non-PD patients. Additionally, total power in PD patients was made up of a significantly higher proportion of HF power and a significantly lower proportion of VLF power than in non-PD patients. No other significant differences in HRV indices were observed. Results suggest that contrary to what has been observed in the majority of PD-only and CAD-only populations; patients with both PD and CAD appear to exhibit lower sympathetic modulation during ordinary daily life conditions. Though preliminary, these findings suggest that changes in HRV may not be the mechanism underlying greater cardiovascular morbidity and mortality among CAD patients with PD.