BACKGROUND: A prospective single-center interventional cohort study was conducted to evaluate the effects of a 5-week comprehensive cardiac rehabilitation program on terms exercise capacity, quality of life, echocardiographic findings and autonomic modulation after first-time myocardial infarction. METHODS: We studied 37 consecutive post-myocardial infartion patients (mean age 66 years). All patients began a 5-week cardiac rehabilitation supervised training. The exercise program consisted of 40 minutes of training, three times a week, on a cycle ergometer at 60-80% of the maximal heart rate. At baseline and after training program we analyzed: the distance walked after the Six-Minutes Walking Test (6MWT); quality of life (QoL) assesed using the Psychological General Well-Being Inventory (PGWBI) questionnaire; echocardiographic finding and autonomic balance assesed heart rate variability (HRV). RESULTS: We observed statistically significant improvement in exercise capacity (from 423+/-94 to 496+/-13 m; P<0.05). Also we observed statistically significant improvements in the many PGWBI dimensions; particularly, anxiety +5.8% (from 18.11+/-5.2 to 19.12+/-4.4); depression +6.0% (from 12.00+/-3.0 to 12.73+/-2.4); positive well-being +6% (from 11.55+/-3.5 to 12.23+/-4.0); general health +10.3% (from 9.48+/-3.5 to 10.46+/-2.87); vitality +6.8% (from 12.96+/-4.2 to 13.85+/-4.2). Finally, we observed changes in HRV indices after training program: RR (from 903+/-169 ms to 952+/-163 ms; P<0.05), pNN50% (from 4.74+/-4.89 to 6.23+/-5.53; P<0.05), in time-domain; LF (from 274+/-169 to 362+/-233 ms2; P<0,05); HF (from 214+/-154 to 314+/-194 ms2; P<0.05) and LF/HF (from 1.53+/-0.54 to 1.24+/-0.47; P<0.05) in frequency-domain. CONCLUSIONS: The study suggest that a cardiac rehabilitation program in postmyocardial infarction improves exercise capacity, QoL and autonomic modulation.