Left ventricular (LV) hypertrophy increases the vulnerability of the myocardium to ischemia. The purpose of this study was to determine whether LV diameter or wall thickness was the principal determinant of the effect of LV mass on the development of ischemia, measured by exercise thallium perfusion imaging, in a population with coronary artery disease (CAD). We studied 109 patients with CAD but no prior myocardial infarction who underwent exercise thallium imaging within 1 year of coronary angiography. Thallium perfusion defects were present in 76% of patients. LV mass index was associated with thallium perfusion abnormalities (odds ratio 2.09 for 50 gm increments), an association that persisted after adjusting for extent of CAD. LV end-diastolic diameter had a strong correlation with a thallium defect (odds ratio 3.7 for 10 mm increments), but LV wall thickness had no correlation (odds ratio 1.0 for 5 mm increments). In a stepwise regression model that included extent of CAD and other potential clinical variables, LV end-diastolic diameter was the strongest predictor of thallium defects (adjusted odds ratio 4.5). This study confirms the association of LV hypertrophy with ischemia in patients with CAD, specifically in patients with eccentric hypertrophy.