BACKGROUND: It is unclear whether advances in management of acute coronary syndrome (ACS) and introduction of novel oral anticoagulants have changed outcomes in patients with ACS with concomitant atrial fibrillation (AF). OBJECTIVE: This study aimed to examine the incidence of AF in patients admitted for ACS and to evaluate its association with adverse outcomes, given the recent advances in management of both diseases. METHODS: Natural language processing search algorithms identified AF in patients admitted with ACS across 13 Northwell Health Hospitals from 2015 to 2021. Hierarchical generalized linear mixed modeling was used to assess the association between AF and in-hospital mortality, bleeding, and stroke outcomes; marginal Cox regression modeling was used to assess the association between AF and postdischarge mortality. RESULTS: Of 12,315 patients admitted for ACS, 3018 (24.5%) had AF with 1609 (53.3%) newly diagnosed. AF patients more commonly received anticoagulation with an oral anticoagulant (80.4% vs 12.3%) or heparin (61.9% vs 56.9%), had lengthier intensive care unit stay (72 vs 49 hours), and underwent fewer percutaneous coronary interventions (31.9% vs 53.1%). In-hospital bleeding, stroke, and mortality were higher in the AF group (15.3% vs 5.0%, 7.4% vs 2.4%, and 6.9% vs 2.1%, respectively). AF was an independent risk factor for all in-hospital outcomes (odds ratios of 2.5, 2.7, and 2.0 for bleeding, stroke, and mortality, respectively) as well as for postdischarge mortality (hazard ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSION: AF is present in 25% of ACS patients and increases risk of in-hospital and postdischarge adverse outcomes. Additional data are required to direct optimal management.