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Atrial fibrillation is common in the setting of acute coronary syndromes (ACS) although its impact on ACS remains controversial.To describe in-hospital management of patients with atrial fibrillation and ACS evaluating the impact of atrial fibrillation on in-hospital and mid-term outcome.We analysed the data of two prospective multicentre nationwide registries (IN-ACS Outcome and MANTRA) to assess clinical characteristics, management, and outcomes of patients with ACS and atrial fibrillation. Study outcomes included death from any cause and a composite end-point of death/re-infarction/stroke/major bleeding within index admission and 6 months’ follow-up.Out of 12 288 ACS patients, 1236 (10.1%) had atrial fibrillation at admission or developed it during hospitalization. Atrial fibrillation patients were older, more often female, and had higher burden of comorbidities. In-hospital mortality was higher among atrial fibrillation patients (8.7 vs. 2.4%, P < 0.001). Patients with atrial fibrillation had a higher incidence of re-infarction (3.5 vs. 1.7%, P < 0.0001) and ischemic stroke (1.7 vs. 0.4%, P < 0.001) compared with those in sinus rhythm. Major bleedings were also more frequent among atrial fibrillation patients (1.9 vs. 0.9%, P < 0.001). In-hospital and at 6 months’ follow-up death from any cause occurred more often in atrial fibrillation patients than in those without atrial fibrillation (9.4 vs. 3.5%, P < 0.0001). At multivariable analysis, atrial fibrillation was an independent predictor of the in-hospital composite end-point (OR 1.67, 95% CI 1.35–2.06, P < 0.0001) but not at 6 months’ follow-up. The independent role of atrial fibrillation on the in-hospital composite end-point was also confirmed by propensity score analyses.Atrial fibrillation was an independent predictor for adverse in-hospital outcome in ACS. This effect disappeared at mid-term follow-up, whereas noncardiac comorbidities emerged as prognostic factors of adverse outcomes.