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OBJECTIVES Severe acute pancreatitis (SAP) is still a big challenge. Accumulated data showed that overexpression of cyclooxygenase-2 (COX-2) in acute pancreatitis and experimental pancreatitis could be attenuated with COX-2 inhibitors. This study was aimed to evaluate whether the occurrence of SAP could be prevented by selective COX-2 inhibitors. METHODS A total of 190 patients with predicted SAP were randomized into convention group or convention plus COX-2 inhibitors (C+COX-2-Is) group. Besides conventional treatment to all patients i