OBJECTIVES: The aim of this study was to determine whether frailty is associated with increased bleeding risk in the setting of acute myocardial infarction (AMI). BACKGROUND: Frailty is a common syndrome in older adults. METHODS: Frailty was examined among AMI patients ≥65 years of age treated at 775 U.S. hospitals participating in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry from January 2015 to December 2016. Frailty was classified on the basis of impairments in 3 domains: walking (unassisted, assisted, wheelchair/nonambulatory), cognition (normal, mildly impaired, moderately/severely impaired), and activities of daily living. Impairment in each domain was scored as 0, 1, or 2, and a summary variable consisting of 3 categories was then created: 0 (fit/well), 1 to 2 (vulnerable/mild frailty), and 3 to 6 (moderate-to-severe frailty). Multivariable logistic regression was used to examine the independent association between frailty and bleeding. RESULTS: Among 129,330 AMI patients, 16.4% had any frailty. Frail patients were older, more often female, and were less likely to undergo cardiac catheterization. Major bleeding increased across categories of frailty (fit/well 6.5%; vulnerable/mild frailty 9.4%; moderate-to-severe frailty 9.9%; p < 0.001). Among patients who underwent catheterization, both frailty categories were independently associated with bleeding risk compared with the non-frail group (vulnerable/mild frailty adjusted odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.23 to 1.44; moderate-to-severe frailty adjusted OR: 1.40, 95% CI: 1.24 to 1.58). Among patients managed conservatively, there was no association of frailty with bleeding (vulnerable/mild frailty adjusted OR: 1.01, 95% CI: 0.86 to 1.19; moderate-to-severe frailty adjusted OR: 0.96, 95% CI: 0.81 to 1.14). CONCLUSIONS: Frail patients had lower use of cardiac catheterization and higher risk of major bleeding (when catheterization was performed) than nonfrail patients, making attention to clinical strategies to avoid bleeding imperative in this population.