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Context Many prior studies have suggested that the majority of deaths in severe acute pancreatitis occur late in the course of the disease as a result of pancreatic sepsis or pancreatic septic-like syndrome. Other have observed that at least half of the deaths occur early as a result of multisystem organ failure. Objective The aim of the present study was to determine the timing of mortality of severe acute pancreatitis and to analyze the course of the disease in a large series of patients. Patients All consecutive patients with a diagnosis of acute pancreatitis admitted to our Centre from October 1984 to December 2000 were retrospectively studied. One thousand one hundred and fifty episodes of acute pancreatitis occurred in 1,135 patients. Main outcome measures Total mortality and frequency of early deaths (less than or equal to 14 days after admission). The clinical features of patients who died were also compared in the early and late mortality groups. Results The overall mortality rate of acute pancreatitis was 4.8% (55 deaths out of 1,135 cases) and when considering the severe forms only, it was13.5% (55 deaths out of 408 cases); 28 deaths (50.9%) occurred within the first two weeks of hospitalization (median day 8, range 2-14) whereas 27 cases (49.1%) occurred after two weeks (median day 28, range 15-56). Early deaths resulted primarily from multisystem organ failure; late deaths occurred mainly from complications in patients having infected necrosis. Conclusion Early deaths in severe acute pancreatitis occur in the half of patients within the first 14 days owing to multi-organ system failure. The remainder of deaths occur later from complications secondary to the infection of pancreatic necrosis; in this subgroup of patients, the association of infected necrosis with organ failure is found frequently.