BACKGROUND: Arrhythmias are common in chronic heart failure and affect outcomes. The incidence and significance of new arrhythmias in acute heart failure, however, are largely unknown. METHODS AND RESULTS: The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations study randomized 949 patients with decompensated heart failure to receive intravenous milrinone or placebo. In the study, patients were divided into 2 groups based on the occurrence of a new arrhythmic event during their index hospitalization and analyzed for outcome. There were 59 new arrhythmic events occurring in 6% of the population. Of these, 49% were atrial fibrillation/flutter. The primary endpoint of days hospitalized for cardiovascular causes within 60 days after randomization was 30.9+/-22.7 for those in the arrhythmia group and 11.3+/-12.7 days for those with no arrhythmias (P=.0001). Mortality during index hospitalization was 26% in the arrhythmia group and 1.8% in the no arrhythmia group (P=.001). Death or hospitalization at 60 days was also worse in the arrhythmia group (35 versus 8.2%, P=.0001; 57 versus 34%, P=.001, respectively). Cox proportional hazard analysis identified new arrhythmias as an independent risk factor for the primary endpoint and death at 60 days. CONCLUSION: New arrhythmia during an exacerbation of heart failure identifies a high-risk group with higher intrahospital and 60-day morbidity and mortality.