Background. Left bundle branch block (LBBB) may occur with or without structural heart disease. In patients with coronary artery disease the presence of LBBB is associated with an increased risk of cardiovascular events. Methods and Results. This study examined the outcome of 293 medically treated patients with LBBB and symptoms who were undergoing stress thallium-201 single photon emission computed tomography imaging. One hundred seventy-three men and 120 women with an age range of 67 ± 9 years and a pretest probability of coronary artery disease of 77% ± 28% were studied. During a mean follow-up of 33 months 58 hard cardiac events (death or nonfatal myocardial infarction) and 112 total events (hard events, coronary angioplasty, coronary bypass surgery, or cardiac transplantation) occurred. Univariate and multivariate Cox survival analysis with clinical, stress, hemodynamic, and single photon emission computed tomography variables identified the perfusion defect size (chi square := 27, p = 0.0001) and increased lung thallium uptake as the most important independent predictors of hard or total cardiac events. The hard event-free survival rate was 91% in patients with no or small defects (< 15% of left ventricular myocardium) and 72% in patients with large defects (p = 0.0001, RR = 3.2, 95% CI 1.7 to 5.9). The total event-free survival rate was 81% in patients with small defects and 48% in patients with large defects (p = 0.0001, RR = 2.7, 95% CI 1.9 to 4.0). The total event rate was 54% in patients with large perfusion defects and increased lung uptake and 17% in patients with no or small abnormality and normal lung thallium uptake (p =0001). Conclusion. Single photon emission computed tomography perfusion imaging is useful in predicting outcome in patients with LBBB and intermediate pretest probability of coronary artery disease. The size of perfusion abnormality and lung thallium uptake stratified patients into high and low risk groups with a threefold difference in hard and total cardiac events.