In the latter half of the 20th century, among participants of the Framingham Heart Study, incidence of heart failure (HF) has declined by about a third in women but not in men and survival after the onset of HF has improved in both sexes; however, HF remains highly lethal with over 50% dying within 5 years after onset of HF. Overall, the 8-year relative risk of HF is 24% lower in women compared with men. The 8-year incidence rates of HF with preserved ejection fraction (HFPEF; EF >45%) and HF with reduced EF (HFREF; EF ≤ 45%) in women and HFPEF in men are similar; however, men have a 2-fold higher cumulative incidence of HFREF than HFPEF. The lifetime risk of HF is about 20% in both women and men at 40, 50, 60, 70, and 80 years of age. Contribution of hypertension and diabetes mellitus to the risk of HF was more prominent in women than in men. Serum levels of several biomarkers were distinctly different in women compared with men and had differential effects on left ventricular structure and function; however, the strength and direction of the association between biomarkers levels and HF risk were generally similar in women and men. In individuals with HF, about two-thirds of the underlying cause of death and about one-half of the immediate cause of death were due to cardiovascular causes. Non-cardiovascular underlying and immediate causes of death were more evident in HFPEF.