The incidence, prognosis, and factors associated with ventricular arrhythmia (VA) in acute coronary syndrome are unknown. We sought to examine the magnitude, predictors, and outcomes of in-hospital VA in patients with acute coronary syndrome. The population comprised 52,380 patients enrolled in the Global Registry of Acute Coronary Events from 1999 to 2005. The proportion who developed VA during hospitalization was 6.9% (1.8% with ventricular tachycardia, 5.1% with ventricular fibrillation or cardiac arrest). The incidence of in-hospital VA decreased over time (8.0% in 1999, 7.0% in 2002, 5.8% in 2005, p <0.001). In-hospital case-fatality rates were higher in patients with versus those without VA (52% vs 1.6%). Several demographic and clinical variables were associated with the occurrence of VA including ST deviation, Killip class, age, initial cardiac markers, serum creatinine and heart rate, and history of selected co-morbidities. Six-month postdischarge mortality was higher in survivors of in-hospital VA versus those who did not develop VA during hospitalization (odds ratio 1.57, 95% confidence interval 1.27 to 1.95). In conclusion, development of VA during hospitalization for acute coronary syndrome was associated with higher in-hospital and 6-month mortalities.