BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects older adults. OBJECTIVES: This study aimed to elucidate the prevalence and prognostic implications of geriatric vulnerabilities across multiple health domains in HFpEF. METHODS: We examined consecutive patients with HFpEF enrolled from the Weill Cornell Medicine (WCM) and the OPTIMISE HFpEF Programs. The primary exposure was the following: multimorbidity, polypharmacy, cognitive impairment, depressive symptoms, frailty, and limited mobility. The primary outcome was a 1-year composite of all-cause hospitalization and mortality. We conducted Cox proportional hazard models to examine associations of the primary outcome with each geriatric vulnerability and the number of impaired domains, adjusting for race and the Meta-Analysis Global Group in Chronic Heart Failure risk score. RESULTS: The WCM cohort included 188 patients with a median age of 76.3 years, the majority of which were NYHA functional class III HF (52.1%); the OPTIMISE cohort included 93 patients with a median age of 79.6 years, the majority of which were NYHA functional class II HF (62.0%). Nearly half of each cohort (42.6% WCM, 46.2% OPTIMISE) had geriatric vulnerabilities spanning all 3 health domains. In fully adjusted models, frailty (WCM: HR: 2.89, 95% CI: 1.65-5.09; OPTIMISE: HR: 2.89, 95% CI: 1.65-5.09) and an increasing number of impaired domains were associated with the primary outcome: with 3 impaired domains conferring a near 4-fold increase in risk (WCM: HR: 3.97, 95% CI: 1.49-10.5, P = 0.007]; OPTIMISE: HR: 3.74, 95% CI: 1.26-11.10, P = 0.017]). CONCLUSIONS: Geriatric vulnerabilities across multiple health domains commonly co-occur in adults with HFpEF and are associated with a worse prognosis.