Background: While the role of hemoglobin in heart failure and renal disease has been investigated, little is known about its effect on clinical exercise test performance and mortality in patients referred for routine exercise treadmill testing (ETT). Hypothesis: Patients with low hemoglobin will have poor exercise capacity and would be at increased risk of mortality and cardiovascular (CV) events. Methods: Clinical variables, laboratory values, and exercise treadmill data were obtained for 1,799 patients referred for routine ETT from 1997 to 2004. All-cause mortality was obtained from the United States Social Security death index and autopsy reports or clinical notes were used to determine CV events and mortality. P values <0.05 were considered significant. Results: Our population had a mean age of 58±12 years, 16% had diabetes, 53% had hypertension, 35% had hypercholesterolemia, and 67% had a history of smoking. During follow-up, 10.3% of patients died, 3.9% of patients died of CV causes, and 11.6% had cardiovascular events. Anemic patients (hemoglobin [Hgb] <13 g/dL) achieved lower metabolic equivalents (METs) than nonanemic patients and had more ST-segment depression (15.5% versus 8.6%, p<0.004). Proportional hazard analysis demonstrated that hemoglobin was significantly associated with all-cause mortality (p<0.0007), CV mortality (p<0.009), and CV events (p<0.01).Kaplan-Meier survival analysis demonstrated that anemic patients had significantly higher mortality and CV events. Conclusion: Hemoglobin is significantly associated with exercise performance, ST-segment depression during ETT, mortality, and cardiovascular events. The incorporation of hemoglobin may add diagnostic and prognostic information to ETT.