OBJECTIVES: L-Asparginase is an essential component of Acute Lymphoblastic Leukemia treatment protocols in pediatric patients which is associated with high survival rates. The treatment cost is expected to vary according to used Asparginase formulation, probability of clinical allergy and probability of silent inactivation. This study aims to compare the cost of two asparginase formulation in the first line setting: PEG-L-Asparaginase and native E.coli L-Asparginase in order to estimate the incremental cost of adapting PEG- Asparaginase in the first line setting from the perspective of a third party payer. METHODS:  A retrospective review of claim data from 2010 to 2014 was conducted to collect resource utilization data and allergy probabilities. Silent inactivation probabilities were estimated from clinical literature. Patients who finished their course of chemotherapy treatment without disease relapse or bone marrow transplantation were included within the analysis. The mean treatment costs were calculated based on patient level data for 67 insured patients. A simulated scenario was performed to calculate the cost of using PEG L-Asparaginase in first line setting. A decision analytical model was run to investigate the cost implication for using PEG L-Asparaginase in high/standard risk patients and low risk patients. RESULTS: The Mean treatment cost of Asparginase in first line setting for low risk patients was $62939.22 and $64003.36 for high/standard risk patients. The mean treatment cost of PEG-Asparginase in first line setting for low risk patients was 79715.68 and $ 82006.23 for high /standard risk patient CONCLUSIONS: Adapting PEG-Asparginase in first line setting is expected to increase the cost of treating ALL patients by $16,777.89 in low risk patient and by 18,003 for high risk patients. The estimated annual budget impact for adapting PEG-Asparginase in first line setting is $226017 per year.