Abnormal heart rate recovery (HRR) after exercise has been associated with increased cardiac mortality. The ability of gated myocardial perfusion single-photon emission computed tomography (SPECT) to evaluate myocardial perfusion and function simultaneously might make it helpful in determining possible mechanisms that are involved in this finding. This study investigated the association between abnormal HRR and other indicators of risk for cardiovascular events. Patients (n = 1,296, 784 men; 57 +/- 11 years of age) who underwent exercise/technetium-99m sestamibi gated myocardial perfusion SPECT at rest were prospectively enrolled. Exercise treadmill testing was performed according to a symptom-limited Bruce's protocol. HRR was obtained from the subtraction of heart rate in the first minute of recovery after exercise treadmill testing from maximal heart rate during exercise. Myocardial perfusion SPECT was semi-quantitatively analyzed using a 17-segment left ventricular model. Left ventricular ejection fraction was automatically calculated using quantitative gated SPECT software. In our study, patients with abnormal HRR were older, more frequently diabetic, and hypertensive and had previous myocardial infarction and myocardial revascularization, higher heart rate at rest and perfusion defect quantification scores, lower left ventricular ejection fraction, and larger left ventricular volumes than did patients with normal HRR. In multivariable analysis, age (p <0.0001), heart rate at rest (p <0.0001), left ventricular ejection fraction (p <0.0001), and perfusion defect extent and severity at rest (p = 0.038) were independent predictors of abnormal HRR. In conclusion, abnormal HRR was significantly associated with lower left ventricular ejection fraction and with perfusion defect extent and severity at rest, but not with gated SPECT markers of myocardial ischemia. Therefore, abnormal HRR may reflect myocardial damage.