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Context The assessment of the severity of pancreatitis is important for proper management of this challenging disease. A highly accurate system which could predict the severity and identify the local extent and complications of a serious inflammation, is beneficial for patient outcome. Objective The aim was to establish the value of the computed tomography severity index in predicting the severity of acute pancreatitis and to compare it with the accuracy of the APACHE II score and serum CRP concentrations. Design Prospective clinical series. Patients Fifty-five consecutive patients (37 women, 18 men; mean age 57 years) with a clinical and laboratory diagnosis of acute pancreatitis. Interventions Clinical evaluation, biochemical analysis of blood and contrastenhanced abdominal CT. Main outcome measures Computed tomography severity index within the first 5 days, serum CRP level, and clinical APACHE II score at 48 hours after admission. Results Thirteen patients had severe pancreatitis according to the Atlanta classification. The mean values of predictive markers in the mild and the severe pancreatitis groups were: computed tomography severity index 1.26 and 6.30 (P<0.001); APACHE II 4.14 and 8.61 (P<0.001); and CRP 96.0 mg/L and 192.4 mg/L (P<0.001), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated for the CTSI (greater than 3: 85%, 98%, 92%, 95%, and 95%), for APACHE II (equal to, or greater than 7: 62%, 86%, 57%, 88%, and 80%) and for CRP (equal to, or greater than 150 mg/L: 85%, 74%, 50%, 94%, and 76%). Conclusion The computed tomography severity index is a reliable method for staging the severity of acute pancreatitis; moreover, CT has the ability of showing the local extent of the inflammation and the occurrence of local complications.