OBJECTIVE: In the last years, a debate exists about type, intensity and frequency of physical exercise that is really indicated to protect healthy subjects from cardiovascular disease. Regular physical training has been associated with an improved cardiovascular risk profile, but it has also been demonstrated that strenuous and uncontrolled physical exercise could be dangerous, in terms of increased cardiovascular morbidity and mortality. In the present study, we evaluated a group of 35 amateur half-marathon runners, who were likewise studied 10 years before (B). The results of B suggested that an increased cardiac sympathetic modulation could potentially represent a negative prognostic factor. The aim of this follow-up was to assess the medium-long-term effects of moderate to vigorous physical training on the cardiovascular neural control, cardiac function and occurrence of cardiovascular diseases. METHODS: Each enrolled subject underwent: (1) an interview and physical examination to ascertain the presence of cardiovascular disease; (2) standing test to evaluate the cardiovascular neural control by means of heart rate variability (HRV), arterial blood pressure (AP) variability and baroreflex sensitivity (BRS); (3) transthoracic echocardiography to evaluate cardiac function. RESULTS: At 10-year follow-up (FU), in this group of middle-aged athletes the occurrence of cardiovascular diseases was low, not unlike that of the overall population. The results of HRV analysis showed a decreased sympathetic and increased vagal modulation directed to the heart, compared with B. In addition, HRV, AP variability and BRS indices showed a physiological response to active standing. Finally, athletes had normal echocardiographic measures. CONCLUSION: We conclude that in our group of athletes a regular moderate-vigorous physical training through the 10 years was quite beneficial as the prevalence of sympathetic cardiac modulation observed at B was not accompanied by increased cardiovascular risk, on the contrary a slight prevalence of vagal indices was observed at FU.