l‐asparaginase is an aminohydrolase that deprives leukemia cells of l‐asparagine required for protein synthesis. Although studies in patients with acute lymphoblastic leukemia have shown that the addition of l‐asparaginase improved the overall remission rate, life‐threatening acute pancreatitis has occurred in 0.5–4% of patients. We describe the first adult case report, to our knowledge, of the successful use of octreotide as a chemoprotectant for the prevention of recurrent pegylated asparaginase (PEG‐ASP)–induced pancreatitis in a 21‐year‐old man with Philadelphia chromosome–negative acute lymphoblastic leukemia. After recurrent PEG‐ASP administration during induction chemotherapy, he developed necrotizing pancreatitis, confirmed by abdominal computed tomography, and further asparaginase therapy was withheld. Currently, there are no specific treatment recommendations for the management of asparaginase‐induced pancreatitis other than drug discontinuation. After disease relapse, a pediatric PEG‐ASP–containing regimen was initiated, and PEG‐ASP therapy was resumed due to its potential clinical benefit. Octreotide 100 μg subcutaneously 3 times/day, utilized as a chemoprotectant, was found to prevent pancreatitis recurrence. The patient completed therapy and was able to receive a bone marrow transplant without further complications from PEG‐ASP therapy. Based on this patient's experience, we believe it is reasonable to reincorporate PEG‐ASP after an episode of pancreatitis with use of octreotide as a chemoprotectant; however, this conclusion will need to be substantiated in a randomized clinical trial with a larger group of patients.