We tested the hypothesis that weight gain would increase arterial stiffness in healthy nonobese adults. To address this, we overfed 14 nonobese men (age: 23+/-1 years) approximately 1000 kcal/d for 6 to 8 weeks until a 5-kg weight gain was achieved. Carotid diameters (high-resolution ultrasound) and pressures (applanation tonometry), body composition (dual energy x-ray absorptiometry), and abdominal fat distribution (computed tomography) were measured at baseline and following 4 weeks of weight stability at each individual's elevated body weight. Overfeeding increased body weight 5.1+/-0.1 kg and body fat 3.4+/-0.4 kg (both P<0.001) in 45+/-7 days. Total abdominal fat increased 46+/-7 cm(2) with weight gain due to increases in both subcutaneous (30+/-6 cm(2)) and visceral fat (15+/-4 cm(2); all P<0.01). As hypothesized, weight gain increased arterial stiffness 13+/-6% and decreased arterial compliance 21+/-4% (both P<0.05). Furthermore, those individuals above the median increase in abdominal visceral fat demonstrated a significantly greater increase in arterial stiffness (0.97+/-0.29 versus 0.06+/-0.36 U; P<0.05) compared with those below the median. Consistent with these observations, the only correlates of the changes in arterial stiffness with weight gain were the increases in total abdominal fat (r=0.794), abdominal visceral fat (r=0.651), and waist circumference (r=0.470; all P<0.05). Taken together, these findings suggest that modest weight gain is associated with increases arterial stiffness in nonobese men. The degree of large artery stiffening with weight gain seems to be determined, in part, by the amount of abdominal visceral fat gain. Importantly, this relation is independent of the amount of total body fat gained.