L-asparaginase (L-asp) is used as part of the initial treatment in children with acute lymphoblastic leukemia (ALL), inducing remission in 83% to 95% of the treated patients. Major toxicity effects reported are hypersensitivity reactions and dysfunctions of the liver and pancreas. Acute pancreatitis (AP) induced by L-asp has been noted in 2.5% to 16% of the treated patients. The purpose of this study was to determine the frequency and outcome of AP in children with ALL treated with L-asp in a tertiary care pediatric hospital. From January 1999 to June 2005, the charts of children with ALL admitted for L-asp treatment were reviewed. Data from children who developed AP were analyzed retrospectively. AP was defined as the presence of clinical data (nausea, vomiting, and abdominal pain), elevated pancreatic enzymes, and changes in the abdominal ultrasound and/or computed tomography (CT) scan. Clinical and biochemical data, abdominal ultrasound, and CT scan findings, complications, treatment, and outcome were analyzed retrospectively. During the last 6 years, 266 ALL new cases were started on chemotherapy including L-asp, of which 18 of 266 (6.7%) developed AP. Pancreatic necrosis by CT scan was found in 10 patients, peripancreatic collections and pseudocyst formation were detected in 5 and 3 cases, respectively, and resolved by cystogastrostomy or drainage. Two patients developed chronic pancreatitis and 3 diabetes. There was no relationship between number of doses and pancreatic toxicity. None of the patient died due to pancreatic toxicity. L-asp is an effective drug to treat ALL, the administration of L-asp requires the monitoring of pancreatic toxicity to detect AP and have treatment initiated as early as possible. Chronic complications after AP occur in almost one third of cases.