Background: A novel method to quantify dyssynchrony using phase analysis of single-photon emission computed tomography (SPECT) myocardial perfusion imaging has been developed. We sought to determine the prevalence of SPECT-derived mechanical dyssynchrony, and we report clinical variables which predict mechanical dyssynchrony in patients with left ventricular dysfunction. Methods: We used a count-based Fourier analysis method to convert the regional myocardial counts from discrete frames per cardiac cycle into a continuous thickening function which allows resolution of the phase of the onset of myocardial contraction. The standard deviation of left ventricular phases (Phase SD) describes the regional phase dispersion as a measure of dyssynchrony. Significant dyssynchrony was defined as Phase SD 43°. 260 patients with left ventricular ejection fraction 35% were examined. Results: The prevalence of mechanical dyssynchrony in the entire cohort of patients studied was 52%. Univariate predictors of Phase SD were age (P = .03), black race (P = .0005), QRS duration, EF, EDV, summed stress score (SSS), and summed rest score (SRS) (all P = <.0001). Black race, male gender, QRS EF, and SRS were independent predictors of SPECT-based mechanical dyssynchrony. Conclusions: Significant SPECT-based mechanical dyssynchrony is relatively common among patients with left ventricular dysfunction. In a population of patients with predominantly ischemic heart disease referred for SPECT, a reduced EF, increasing QRS duration, severity and extent of myocardial scar on SPECT imaging are independent predictors of mechanical dyssynchrony and may serve to identify patients for dyssynchrony screening. © 2010 American Society of Nuclear Cardiology.