Limited data exist on the course of left ventricle ejection fraction (LVEF) among outpatients with heart failure (HF) and preserved ejection fraction (HFpEF) and its impact on outcomes. We evaluated 322 consecutive outpatients with confirmed HF, LVEF >40%, no previous LVEF ≤40%, and no specific cardiomyopathies or primary right-sided or valvular heart disease. Median age was 73 years (interquartile range: 63 to 82); 57.1% were women, 50.3% White, and 45.0% Black; median LVEF was 55% (50% to 60%); and 45.6% had coronary artery disease. After a median of 37 months (32 to 38) and 4.5 follow-up echocardiograms (4 to 6) per patient, 11.4% of patients (95% confidence interval [CI] 5.2% to 17.7%) developed LVEF <40%. The average drop in LVEF among these patients was 19.4 units (95%CI 15.0 to 23.8) to an average LVEF of 30.3% (95%CI 27.4% to 33.2%). Baseline systolic blood pressure >130 mm Hg was associated with more LVEF decline. During follow-up, 50 patients died (3-year mortality 15.3%) and 67 additional patients were hospitalized for HF (3-year death plus HF hospitalization 35.6%). Development of LVEF <40% was subsequently followed by 5-fold higher mortality in time-updated models (adjusted HR 4.91; 95%CI 2.00 to 12.0; p = 0.001) and 3.5-fold higher rates of death or HF hospitalization (adjusted HR 3.70; 95%CI 1.67 to 8.19; p = 0.001). Interval coronary events were infrequent (10%) among patients with deteriorated LVEF. The impact of LVEF changes on outcomes was similar in White and Black patients. In conclusion, a proportion of patients with HFpEF will develop reduced LVEF over time. These patients have worse prognosis subsequently.