Background Although approximately 50% of heart failure patients are reported as heart failure with preserved left ventricular systolic function (HFPSF), echocardiographic prognostic predictors have not been well investigated. Recently, the tissue Doppler-derived index, the ratio of the early transmitral flow velocity and the early mitral annular velocity (E/E'), was reported as useful in predicting prognosis of patients with heart diseases. The purpose of this study was to investigate whether E/E' predicts prognosis in HFPSF. Methods and Results A total of 50 patients with HFPSF (ejection fraction >50%) were consecutively enrolled and studied. Echocardiographic examination was performed on admission and repeated after optimized medical therapy. Cardiac events were defined as death and unplanned hospitalization because of congestive heart failure. Cardiac event-free survival curves from patients with E/E' >15 and E/E' ≤15 at baseline did not differ. On the other hand, patients with E/E' >15 after medical therapy showed significantly lower cardiac event-free survival than patients with E/E' ≤15 (log-rank, P=0.005). By multivariate logistic regression analysis, E/E' >15 after medical therapy was the only independent predictor of cardiac events (P=0.037, risk ratio=6.1, 95% confidence interval: 1.12-33.3) in patients with HFPSF. Conclusions Elevated E/E' after optimized medical therapy may be useful in predicting cardiac events in patients with HFPSF. (Circ J 2009; 73: 86 -91)