This study examines a national cohort of patients with a diagnosis of acute coronary syndrome (ACS) for the prevalence of frailty, temporal changes over time, and its association with treatments and clinical outcomes. The National Inpatient Sample database was used to identify US adults with a diagnosis of ACS between 2004 and 2014. Frailty risk was determined using a validated Hospital Frailty Risk Score based on ICD-9 codes using the cutoffs <5, 5 to 15, and >15 for low- (LRS), intermediate- (IRS), and high-risk (HRS) frailty scores, respectively. Logistic regression assessed associations of frailty with clinical outcomes, adjusted for patient co-morbidities and hospital characteristics. From 7,398,572 hospital admissions with ACS between 2004 and 2014, 86.5% of patients had LRS, 13.4% had an IRS, and 0.1% had an HRS. From 2004 to 2014, the prevalence of IRS and HRS patients increased from 8.1% to 18.2% and 0.03% to 0.18%, respectively (p <0.001 for both). The proportion of patients treated with percutaneous coronary intervention was greatest among patients with lowest frailty risk scores (LRS 42.9%, IRS 21.0%, and HRS 14.6%). Comparing HRS to LRS, there was a significant increase in bleeding complications (odds ratio [OR] 2.34, 95% confidence interval [CI] 2.03 to 2.69), vascular complications (OR 2.08, 95% CI 1.79 to 2.41), in-hospital stroke (OR 7.84, 95% CI 6.93 to 8.86), and in-hospital death (OR 2.57, 95% CI 2.18 to 3.04). Risk of frailty is common among patients with ACS, is increasing in prevalence, and is associated with differential management strategies, and outcomes during hospitalization. Increased awareness could facilitate frailty-tailored care to minimize the risk of adverse outcomes.