There was no documented link between social isolation and a lack of social network linkages in older adults. The knowledge gap was critical because the risk of heart failure (HF) and social isolation increases with age. The research looked at whether social isolation was linked to HF in older women and depressive symptoms as a possible mediator and age, race, and ethnicity as effect modifiers. The Women’s Health Initiative (WHI) research comprised 44,174 postmenopausal women of various races and ethnicities assessed annually for HF adjudication from baseline enrolment (1993–1998) to 2018. The investigators used mediation research to look at painful symptoms as a possible mediator, and they looked at how impact modification differed by age, race, and ethnicity. The major outcome was incident HF necessitating hospitalization. Social isolation was measured using a composite variable that included marital/partner status, religious affiliations, and community links. CESD (Center for Epidemiology Studies of Depression) was used to assess depressive symptoms. Researchers reviewed data from 36,457 women over a median follow-up of 15.0 years and found 2,364 (6.5%) incident HF cases, as well as 2,510 (6.9%) participants who were socially isolated. Socially isolated women had a greater risk of incident HF than nonisolated women in multivariable analyses adjusted for sociodemographic, behavioral, clinical, and general health/functioning (HR, 1.23; 95% CI, 1.08–1.41). The link remained unchanged when depressive symptoms were included in the model (HR, 1.22; 95% CI, 1.07–1.40). Race, ethnicity, or age, the relationship between social isolation and incident HF was not attenuated by race, ethnicity, or age. Independent of established HF risk factors, socially isolated older women were at an elevated risk of developing HF.