OBJECTIVE: To assess the acute response of cardiac autonomic modulation (ACAM) during and after a session of virtual reality-based therapy (VRBT) compared to a session of conventional cardiovascular rehabilitation (CR) and to evaluate the effects of 12 weeks of training on this response. METHODS: We assessed 28 volunteers (63.4 +/- 12.5 years). The ACAM was judged by linear indexes of heart rate variability (HRV) in VRBT and CR sessions. Later, patients completed 12 weeks of VRBT+CR and the assessment was repeated at the 12(th) week. RESULTS: Throughout the 1(st) VRBT session vagal withdrawal occurred (RMSSD/HFnu); sympathetic nervous system stimulation (LFnu) and progressive decrease of global HRV (SDNN). During the recovery, the SDNN, HFnu, and LFnu improved from the 5(th)minute on both therapies. After 12 weeks, the LFnu, HFnu, and the LF/HF-ratio revealed no significant changes in Ex3-Ex4 equated to Rep during VRBT. In recovery, the HFnu and LFnu improved before the 5(th)minute on both therapies. CONCLUSIONS: ACAM during and after the VRBT was comparable to CR, yet, the extents were greater in the VRBT. After 12 weeks of VRBT training, the subjects adapted to the exercises from the 15(th)minute and exhibited faster recovery of HFnu and LFnu indexes compared to the 1(st) week.