Objectives: The aim of this study was to determine whether single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is an effective method of risk stratification for sudden cardiac death (SCD) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) >35%. Background: Most victims of SCD have an LVEF >35%. Methods: The study population included 4,865 patients with CAD and LVEF >35% who underwent gated SPECT MPI. We used Cox proportional hazard modeling to examine the relationship between patient characteristics and SCD. Results: The median age of the population was 63 years (25th, 75th percentile: 54, 71 years), and the median LVEF was 56% (25th, 75th percentile: 50%, 64%). The median follow-up for all patients was 6.5 years (25th, 75th percentile: 3.6, 9.3 years). During follow-up, there were 161 SCDs (3.3%). After multivariable adjustment, LVEF, the Charlson index, hypertension, smoking, antiarrhythmic drug therapy, and the summed stress score (SSS) were associated with SCD (all p < 0.05). For each 3-U increase in the SSS, the hazard ratio for SCD was 1.13 (95% confidence interval: 1.04 to 1.23). The addition of perfusion data to the clinical history and LVEF was associated with increased discrimination for SCD events (c-index 0.728). Risk stratification with a derived SPECT nomogram did not result in statistically significant net reclassification improvement (p = 0.26) or integrated discrimination improvement (p = 0.38). Conclusions: Among patients with CAD and LVEF >35%, the extent of stress MPI perfusion defects is associated with an increased risk of SCD. Future large prospective studies should address the role of perfusion imaging in the identification of high-risk patients with LVEF >35% who might benefit from ICD implantation. © 2010 American College of Cardiology Foundation.