The aim of the study was to determine the influence of the previous use of digoxin on the hospital mortality and complications of patients admitted because of acute coronary syndrome (ACS). We analyzed the data of patients included in the ARIAM-Andalucia Registry, which involves 49 hospitals in Andalucia, Spain, from 2007 to 2012. Patients on digoxin treatment prior to their admission because of ACS constituted the digoxin group (DG), and were compared with the group of patients not on digoxin. Logistic regression and propensity score matching were used to analyze the differences. We included 20,331 patients, of whom 244 (1.2 %) were on digoxin. DG patients were older (73.1 vs 63.7 years old), more often women, and had more diabetes, hypertension, previous myocardial infarction, heart failure, stroke, atrial fibrillation, peripheral vascular disease, obstructive pulmonary disease or kidney disease. On univariate analysis, DG patients had significantly higher hospital mortality (13.5 vs 5.3 % P < 0.001), and more cardiogenic shock, but less ventricular fibrillation, and no differences in atrioventricular block, stroke or reinfarction. After the multivariate analysis, DG had no significant influence on hospital prognosis [odds ratio (OR) 1.21, 95 % confidence interval 0.79-1.86]. The analysis of a propensity-matched cohort of 464 patients (232 DG and 232 NoDG) did not find differences in hospital mortality (13.4 vs 13.4 %) nor other complications. In our cohort of ACS patients, the previous treatment with digoxin was not associated with an increase in dysrhythmic complications nor was an independent predictor of mortality during hospitalization.