Introduction: We have investigated the potential relationship between cardiac autonomic activity and accelerated idioventricular rhythm (AIVR) in response to reperfusion in the setting of an acute myocardial infarction (AMI) through spectral analysis of heart rate variability (HRV). Methods and Results: We studied 16 patients with AMI who developed spontaneous sustained AIVR after initiation of intravenous thrombolysis. Sympathovagal interactions were evaluated by analysis of the low- (LF) and high-frequency (HF) spectral components of HRV for each 5-min interval over the 30-min periods preceding and following AIVR. The occurrence of AIVR was related to the ST-segment elevation resolution and the angiographic evidence of restored coronary flow to assess timely reperfusion and sustained coronary artery patency. The analysis of spectral components over time revealed combined responses of both autonomic limbs preceding and following AIVR, which were not followed by corresponding changes in heart rate. Ten minutes before AIVR, there was a characteristic continuous increase in LF, in the setting of a concomitant withdrawal of HF, suggestive of a progressive sympathetic predominance. After the end of AIVR, the opposite pattern was found with an increased HF and decreased LF, indicative of parasympathetic rebound overactivity. All patients showed signs of fast reperfusion and complete restoration of coronary flow. Conclusion: Our results indicate that reperfusion-induced AIVR is modulated by sympathetic stimulatory effects, whereas a counterregulatory vagal response seems to exert a profound effect upon its suppression. Clinically, the occurrence of early sustained AIVR appears to offer reliable information about both timely reperfusion and sustained and effective coronary artery patency.