Hypertrophy of the left ventricle is a diagnostic dilemma in subjects who engage in regular endurance exercise. We studied prospectively whether endurance training in previously sedentary young and middle-aged men and women can alter left ventricular (LV) characteristics. We recruited 33 healthy young and middle-aged subjects (18 women, 15 men, ages 21 to 59 years) to undergo 12 weeks of home-based brisk walking and jogging at a target heart rate ≥120 beats/min for ≥30 minutes 3 times a week. LV characteristics were measured by cine magnetic resonance imaging. Training intensity as estimated by heart rate correlated positively with the increase in LV myocardial area (r = 0.51, p = 0.005) in the 28 men and women completing the study. In the 13 men and women who trained with heart rate of ≥120 beats/min, LV myocardial area was larger after than before training (17.7 ± 2.9 vs 16.8 ± 2.8 cm 2, p <0.05). Moreover, in these subjects LV myocardial area increased more (5.5 ± 9.0% vs −3.0 ± 5.0%) than in the 15 men and women who trained at a lower intensity (p <0.05). LV end-systolic and end-diastolic area and ejection fraction did not change significantly. In conclusion, moderate-to-vigorous endurance training at moderate volumes does not influence LV end-diastolic volume or ejection fraction, but has a minor influence on LV hypertrophy in previously sedentary young and middle-aged men and women.