BackgroundMyocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is characterized by clinical evidence of myocardial infarction with nonobstructive coronary stenosis on angiography (stenosis < 50%). Studies on the effect that exercise-based cardiac rehabilitation (CR) has on outcomes in MINOCA patients are lacking. Therefore, the purpose of this study was to determine the effect of exercise-based CR on clinical outcomes in patients with MINOCA. MethodsA total of 524 participants with MINOCA were recruited in this prospective cohort study from August 2014 to October 2016 and followed for three years. We randomly divided 524 patients into an exercise-based cardiac rehabilitation group (CR+) and a control group (CR−). The CR+ group followed a home-based exercise-training program three times a week during the three years of moderate continuous training (MCT; 65%–75% of peak heart rate) on a bicycle or treadmill. ResultsAfter one year of follow-up, the Short Form 36 (SF-36) survey showed apparent improvement in the mean physical health score in the CR+ group compared with the CR− group (P < 0.01). During the three-year follow-up, all-cause mortality occurred in 60 individuals, and major adverse cardiovascular events (MACE) happened in 136 individuals. Kaplan-Meier curves indicated a significant reduction in all-cause mortality (log-rank P < 0.05) and MACE (log-rank P < 0.01) in the CR+ group. A multivariate Cox regression analysis indicated that exercise-based CR was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.483; 95% confidence interval [CI], 0.279–0.818; P < 0.01) and MACE (HR = 0.574; 95% CI, 0.403–0.827; P < 0.001). ConclusionsA long-term exercise-based CR program was associated with superior physical health and a significant reduction in all-cause mortality and MACE in patients with MINOCA.