Pegaspargase, a pegylated form of native Escherichia coli-derived L-asparaginase, is indicated for treating acute lymphoblastic leukemia (ALL) as a component of multi-agent chemotherapy. Although it has been approved for marketing, real-world, long-term safety information in children is still lacking. We aimed to investigate the adverse events (AEs) caused by Pegaspargase through data mining of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, thereby providing a reference for clinical safety in pediatric populations. A disproportionality analysis was conducted to quantify the correlation between Pegaspargase and AEs, using four algorithms. Subgroup analyses were performed to identify differences between AEs in different clinical characteristics, aiming to assess the risk factors in Pegaspargase-associated pancreatitis. Among 21,161,817 reports, 847 implicated Pegasparagase as the primary suspected drug, uncovering AEs across 26 organ systems. Notably, we identified four previously unlisted AEs. Furthermore, the occurrence of pancreatitis-related is closely related to the age (χ ² = 8.219, p < 0.05). This research offers a new viewpoint on clinical safety evaluations related to Pegasparagase and provides some references for improving the safety of clinical medication in pediatric populations.