During voluntary contractions, the skeletal muscle of healthy older adults often fatigues less than young adults, a result that has been explained by relatively greater reliance on muscle oxidative metabolism in the elderly. Our aim was to investigate whether this age-related fatigue resistance was eliminated when oxidative metabolism was minimized via ischemia induced by cuff (220 mmHg). We hypothesized that 1) older men (n=12) would fatigue less than young men (n=12) during free-flow (FF) contractions, 2) both groups would fatigue similarly during ischemia, and 3) reperfusion would re-establish the fatigue resistance of the old. Subjects performed 6 min of intermittent, maximal voluntary isometric contractions of the ankle dorsiflexors under FF and ischemia-reperfusion (IR) conditions. Ischemia was maintained for the first 3 min of contractions, followed by rapid cuff deflation and reperfusion for 3 additional minutes of contractions. Central activation, peripheral activation, and muscle contractile properties were measured at 3 and 6 min of contractions. Older men fatigued less than young men during FF (p&#8804;0.02), ischemia (p<0.001) and reperfusion (p<0.001). During FF, activation and contractile properties changed similarly across age groups. At the end of ischemia, central (p=0.02) and peripheral (p&#8804;0.03) activation declined more in the young, with no effect of age on the changes in contractile properties. Thus, age-related fatigue resistance was evident during FF and IR, indicating that differences in blood flow and oxidative metabolism do not explain the fatigue resistance of old age.