Introduction: Exercise training with well-known health benefits is a key element in the self-management of coronary artery disease (CAD). Although current guidelines for patients with CAD recommend daily exercise training, most of the patients do not follow the guidelines. We tested the hypothesis that an exercise training program guided by a novel technology used at home will improve adherence to exercise training. Methods: One to three weeks after percutaneous coronary intervention (PCI), acute coronary syndrome patients (n = 50) were randomized into traditional (age 65 ± 8years) and novel technology-guided (age 60 ± 8years) exercise rehabilitation groups. The novel technology included a tablet computer with a virtual autonomous physiotherapy agent (VAPA group) for every patient at home; it was used to guide exercise training time, volume, and intensity. Traditional rehabilitation was performed by exercise training prescriptions, phone calls, and diaries (control group). The duration of the rehabilitation program was 6months for both groups. Exercise capacity and 24-h heart rate variability were measured at baseline and at the end of the program. Adherence to exercise was measured over 6months as the percentage of realized training. Results: None of the patients dropped out from the VAPA group, while three patients dropped out from the control group. Adherence to exercise was higher in the VAPA group than in the control group for resistance training (141% ± 56% vs. 50% ± 20%, p < 0.0001), and there were no differences between the groups for aerobic training (144% ± 45% vs. 119% ± 65%, p = 0.22). Exercise capacity increased in both the groups (time p < 0.001, time × group interaction p = ns). High-frequency power of R-R intervals (lnHF) increased in the VAPA group but remained unchanged in the control group (natural logarithm of lnHF power from 5.5 ± 0.7 to 5.8 ± 0.9ms2 and from 5.3 ± 0.8 to 5.2 ± 0.7ms2, respectively, time × group interaction p = 0.014). Conclusion: Compared with the use of traditional methods, the use of novel technology at home results in better adherence to exercise, particularly in resistance training, in acute coronary syndrome patients. Second, the VAPA group showed improved cardiac vagal regulation, documented by increased vagally mediated R-R interval fluctuation, compared with the traditional training group (ClinicalTrials.gov identifier: NCT03704025).