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Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatitis Study (SAPS) database was reviewed. Patients Four out of 102 enrolled patients fulfilled the above sequence of events: progression from a single self-limited episode of acute pancreatitis to recurrent attacks to chronic pancreatitis proven by CT scan. However, not all 102 enrolled patients were followed with CT scans; hence there may be more patients with progression. Results In all four patients, upon initial presentation, there was no evidence of chronic pancreatitis on the CT scan performed and no clear acute pancreatitis etiology was identified. They were asymptomatic between recurrent attacks. All patients progressed to chronic pancreatitis over a relatively short period of time. Two patients were positive for SPINK1 mutations (N34S), and underwent pancreatectomy with pancreatic islet autotransplantation. Conclusion The presented patients seem to fulfill the sentinel acute pancreatitis event hypothesis. Their clinical course supports the concept that pancreatitis may be an entity with a broad spectrum of end-points ranging from an isolated episode of acute pancreatitis evolving to chronic pancreatitis.