Exogenous fructose 1,6-diphosphate (FDP), a glycolytic intermediate, increases blood ATP and 2,3 diphosphoglycerate levels, facilitates the dissociation of oxygen from hemoglobin, and increases red blood cell flexibility. These mechanisms explain why it has been effective in enhancing energy production in a variety of ischemic conditions. The present study was undertaken to determine whether FDP could enhance oxygen supply and thus improve exercise performance in patients with peripheral vascular disease. Ten male patients (mean age 63 ± 5 years) with peripheral vascular disease performed symptom-limited exercise testing after randomized, double blind infusion of either 200 mg/kg body weight FDPO or placebo. Data were evaluated at rest, at a matched submaximal workload (2-3 MPH/0% grade), and at peak exercise, defined as the occurrence of moderately severe claudication. No differences were observed in heart rate, blood pressure, gas exchange data, time to the onset of claudication or peak exercise, or lactate and 2,3 diphosphoglycerate levels. In contrast to previous studies performed among patients with peripheral vascular disease and other studies using more severe hypoxic conditions, FDP did not affect the respiratory gas exchange or exercise capacity of patients with exertional claudication.