BACKGROUND: The estimation of left ventricular (LV) filling pressure from the ratio of transmitral and annular velocities (E/e') after exercise echocardiography may identify diastolic dysfunction in patients who complain of exertional dyspnea. This study sought to determine the relative contributions of exercise E/e' and ischemia to outcomes in patients referred for exercise echocardiography. METHODS AND RESULTS: Rest and exercise E/e' were obtained in 522 patients referred for exercise echocardiography, who were followed for cardiovascular death and hospitalization over a median of 13.2 months. Exercise E/e' >2 SD from normal was used to denote raised LV filling pressure with stress (n=75), and ischemia (n=250) was identified by inducible wall motion abnormalities. There were 65 cardiovascular hospitalizations during the follow-up period. Survival analysis showed patients without ischemia and with normal exercise E/e' to have a better prognosis than those with ischemia, with or without raised exercise E/e' (P=0.003) and the outcomes of patients with isolated raised exercise E/e' and isolated ischemia to be similar. Exercise E/e' was most valuable in patients with normal resting E/e'; those with elevation with exercise had a worse outcome than those with normal exercise E/e' (P=0.014). Exercise capacity (hazard ratio, 0.893; P=0.008), exercise wall motion score index (hazard ratio, 1.507; P<0.001), and exercise E/e' >14.5 (hazard ratio, 2.988; P=0.002) were independent predictors of outcome. The addition of exercise E/e' to exercise capacity and wall motion score index resulted in an increment in model power to predict adverse outcome (P=0.006). CONCLUSIONS: Exercise E/e' is associated with cardiovascular hospitalization, independent of and incremental to inducible ischemia.