Background: Abnormal coronary and brachial artery responses have been described in individuals with risk factors for coronary artery disease (CAD). Peripheral arterial tonometry (PAT), a newly developed digital plethysmographic technique was used to assess peripheral vascular response to exercise in healthy controls and individuals with risk factors. Methods and Results: Continuous finger PAT during Bruce protocol exercise test was performed in 30 subjects with risk factors for CAD and 30 healthy individuals. Compared with baseline, the PAT wave amplitude at peak exercise decreased in the subjects but increased in the controls: 83 ± 28% vs. 114 ± 40% respectively, p < 0.01. Conclusions: A different pattern of systemic vascular response to exercise was found in individuals with risk factors for atherosclerosis. Since the vascular behavior in these patients is probably related to endothelial dysfunction, it may be that peripheral arterial tonometry can be used as a simple, readily available technique to assess endothelial function.