Our objective was to analyze conservative management in a large series of acute necrotizing pancreatitis (ANP) patients in a specialized center for pancreatic disease in the Internal Medicine and Emergency Department of a 1,500-bed hospital. One hundred ninety-nine patients with ANP were considered (mean age, 55.4 +/- 18.2 years; biliary etiology, 60.3%). Identification of necrotizing forms of acute pancreatitis was obtained by ultrasonography, computed tomography scan, and surgery (53 cases). Exclusion of infection of the necrosis was based on clinical findings and percutaneous aspiration with bacteriological sampling. Medical treatment was started in all cases; 37 patients required ICU treatment; 87 patients underwent early endoscopic cholangiopancreatography (ERCP), and endoscopic sphincterotomy was performed in 61 cases; and percutaneous guided aspiration of necrosis and fluid collections was performed in 78 cases and in 9 patients with acute pseudocysts. Fifty-three patients (26.6%) underwent surgery; all patients (n = 30) with infected necrosis were in this group. One hundred forty-six patients were unoperated (73.3%): clinical resolution of ANP and biochemical normalization was achieved in 132 cases (66.3%) at discharge. Ultrasonographic follow-up documented morphological resolution of necrosis and fluid collections in 84 cases (57.5%) at different periods from the onset of ANP (range, 2.2-63.5 weeks); 16 patients dropped out and seven patients are still being followed. Spontaneous regression of acute pseudocysts was observed in 59.2%; percutaneous/endoscopic aspiration was successful in 33.3%. Mortality was 9.5%, significantly lower than the mortality observed in operated patients (28.3%; p = 0.002). Conservative treatment of ANP with sterile necrosis may allow healing in most cases, independent of the extent of necrosis or its association with major complications.