Physical activity (PA) may modify cardiovascular structure and function as well as insulin sensitivity and level of plasma adipokines in relation to its extent, duration, and intensity. To evaluate the associations of average daily PA and bouts of moderate-to-vigorous-intensity PA with cardiovascular and metabolic measures, 45 healthy volunteers (mean age = 42 ± 9 years) not involved in regular intensive exercise training and competitive sport activity underwent the following examinations: (1) accelerometer monitoring of ambulatory movements (average monitoring time = 6.1 ± 1.3 days); (2) complete carotid and cardiac ultrasound; (3) measurement of carotid-femoral pulse-wave velocity; (4) anthropometric measurements; (5) euglycemic hyperinsulinemic clamp; and (6) assessment of plasma levels of leptin, adiponectin, and high-sensitivity C-reactive protein (hsCRP). Average PA measured by accelerometer correlated with carotid beta-stiffness index (inversely) and with longitudinal systolic myocardial velocity (directly), independently of age, anthropometric, hemodynamic, and metabolic parameters. Subjects with periods of moderate-to-vigorous-intensity PA lasting at least 10 min (n = 28) had higher left ventricular (LV) mass index and lower plasma adiponectin, leptin, and hsCRP (P < 0.05 for all) compared with those who spent the monitoring time only in sedentary and light-intensity PA (n = 17). Minutes per day spent in moderate-to-vigorous PA correlated with LV mass index (directly) and with plasma adiponectin (inversely). Plasma adiponectin was an independent determinant of LV mass, together with body surface area, stroke volume, and systolic blood pressure (cumulative r (2) = 0.80). We conclude that in healthy subjects, average daily PA is independently related to longitudinal systolic myocardial function and to local carotid stiffness. Bouts of moderate-to-vigorous PA seem to induce LV mass increase, which may be partially related to a decrease in plasma adiponectin level.