Pulse pressure amplification (i.e., the ratio of peripheral to central pulse pressure) is a strong predictor of cardiovascular events. Circulating free fatty acid, which is a major cause of insulin resistance, has been reported to favorably be associated with pulse pressure amplification in the arm (from the aorta to brachial artery). We hypothesized that this paradoxical relationship depended on an evaluating site of pulse pressure amplification and investigated whether serum free fatty acid level is related to pulse pressure amplification in the arm or trunk (from the aorta to femoral artery) in overweight/obese men. In a cross-sectional study, 85 men participated, and regression analyses revealed that serum free fatty acid level was significantly and independently associated with pulse pressure amplification in the arm but not the trunk. In a longitudinal study, 33 men completed a 12-week lifestyle intervention that involved both exercise training and dietary modification. The lifestyle intervention-induced change in serum free fatty acid level was significantly correlated to that in pulse pressure amplification in the arm but not the trunk. These results support our hypothesis and suggest that pulse pressure amplification should be measured in the trunk instead of the arm in overweight/obese men to simplify its interpretation.