Aspirin resistance as defined by failure to effectively inhibit thromboxane synthesis is associated with a higher risk of recurrent myocardial ischemia and cardiovascular death. Heart rate variability (HRV) analysis has been extensively used to identify patients at risk for increased cardiac mortality. The aim of this study was to evaluate the association between HRV and aspirin resistance in patients with stable coronary artery disease (CAD). Sixty-nine (69) consecutive patients with stable CAD were included in this study. Of the 69 patients, 18 (26%) were aspirin nonresponders. When the aspirin responders were compared with the nonresponders, there was no significant difference between the groups with respect to most clinical parameters, major cardiovascular risk factors, medical treatments, and aspirin dosages. However, the patients with aspirin resistance had a higher previous myocardial infarction history and lower left ventricular ejection fraction. Moreover, mean platelet volume, CT/ EPI, CT/ADP values, LF and LF/HF ratio were higher while HF, SDNN, SDANN, and RMSSD were lower in the nonresponder group than the responders. Regarding HRV parameters, CT/ADP time was negatively correlated with SDNN (r = -0.5, P = 0.02) and HF (r = -0.4, P = 0.03), and positively correlated with LF (r = 0.6, P = 0.01) and LF/HF (r = 0.7, P = 0.001). Similarly, CT/EPI time was negatively correlated with SDNN (r = -0.4, P = 0.03), and positively correlated with LF (r = 0.5, P = 0.02) and the LF/HF ratio (r = 0.5, P = 0.02). Regression analysis revealed that the only parameters affecting SDNN and LF/HF ratio were left ventricle ejection fraction and aspirin resistance. The heart rate variability decreased and sympathetic activity increased in the patients with aspirin resistance and stable CAD. This may contribute to a higher risk of recurrent myocardial ischemia and cardiovascular death in patients with aspirin resistance.