Background: Hypoglycemia is a rarely reported complication of Asparaginase (ASP) therapy in children with lymphoblastic leukemia/lymphoma (ALL/LLy). We sought to identify risk factors and outcomes among patients with ASP-induced hypoglycemia (AIH) at our institution. Methods: Retrospective cohort study using electronic medical records to identify all patients who received ASP and had diagnosis of hypoglycemia between 6/1/2017-6/30/2022. Demographic and clinically relevant data were collected. Results: A total of 672 patients received ASP, with 8% having AIH–defined by a measured low blood glucose level within 14 days of ASP administration and other causes of hypoglycemia excluded. Median age at ALL/LLy diagnosis was 4.4 years (Interquartile range [IQR]: 2.5 – 7.7) which was younger than patients without AIH (median 6.9 years, p-value 0.005), and median BMI z-score 0.50 (IQR: -0.46 – 0.95). Initial hypoglycemia event was during Induction therapy in 71%, with median time from ASP to hypoglycemia diagnosis of 11 days (IQR: 6-15). Median duration of the hypoglycemia episode was 11 days (IQR: 7-19). Recurrent hypoglycemia with subsequent ASP doses occurred in 84% of patients, with a median duration 14 days (IQR: 8-21). Overall survival of the AIH cohort was 80% (85% if limited to patients with newly diagnosed ALL/LLy), with 3 years’ median follow up. In univariate analysis, hypoglycemia severity was not associated with age, sex, ethnicity, or weight. Conclusion: AIH is relatively common with no clear risk factors besides younger age. It can recur and become more severe with longer duration. AIH screening and management should be implemented.