Background-Diastolic dysfunction is an independent predictor of mortality in patients with normal left ventricular ejection fraction. There are limited data, however, on whether worsening of diastolic function is associated with worse prognosis. Methods and Results-We reviewed clinical records and echocardiograms of consecutive patients who had baseline echocardiograms between January 1, 2005, and December 31, 2009, that showed left ventricular ejection fraction ≥ 55% and who subsequently had a follow-up echocardiogram within 6 to 24 months. Diastolic function was labeled as normal, mild, moderate, or severe dysfunction. All-cause mortality was determined by use of the Social Security Death Index. Kaplan-Meier survival analysis and Cox regression analysis with a proportional hazard model were performed to assess outcomes. A total of 1065 outpatients were identified (mean± SD age, 67.9± 13.9 years; 58% male). Baseline diastolic dysfunction was present in 770 patients (72.3%), with mild being the most prevalent. On follow-up testing (mean± SD, 1.1± 0.4 years), 783 patients (73%) had stable, 168 (16%) had worsening, and 114 (11%) had improved baseline diastolic function. Eighty-eight patients (8.3%) had a decrease in left ventricular ejection fraction to < 55% and were more likely to have advanced diastolic dysfunction (P=0.002). After a mean± SD follow-up (from the second study) of 1.6± 0.8 years, 142 patients (13%) died. On multivariate analysis, a decrease in left ventricular ejection fraction to < 55% and any worsening of diastolic function were independently associated with increased risk of mortality (hazard ratio, 1.78; 95% confidence interval, 1.10-2.85; P=0.02; and hazard ratio, 1.78; 95% confidence interval, 1.21-2.59; P=0.003, respectively). Conclusion-In patients with normal baseline left ventricular ejection fraction, worsening of diastolic function is an independent predictor of mortality.