OBJECTIVES:  Acute Lymphoblastic Leukaemia (ALL) is the most commonly diagnosed neoplasia in patients under 15 years of age. In Spain, incidence and prevalence rates are 1.45 and 7.00 per 100,000 inhabitants per year, respectively. Native asparaginase is an effective treatment for patients with ALL, but it is associated with a high incidence of hypersensitivity reactions. When these occur, crisantaspase therapy is administered. Pegaspargase (Oncaspar®) is an asparaginase form that provides comparable efficacy to native asparaginase, lower administration frequency, and a decreased incidence of hypersensitivity reactions. METHODS:  We carried out a cost minimization analysis comparing the costs native asparaginase therapy vs pegaspargase therapy. We assumed crisantaspase is administered in case of hypersensitivity reactions with any of the compared alternatives. Probabilities of hypersensitivity reactions were 41% for native asparaginase and 12% for pegaspargase. The perspective was that of the Spanish National Health System and the time horizon was 30 weeks. We included pharmaceutical costs (pegaspargase: 1 vial with 3,750 UI at 1,550€, dose 1000 UI/m2; native asparaginase: 10 vials with 10,000 UI at 528.9€, dose 10,000 UI/m2; crisantaspase: 10,000 UI at 3,952€, dose 20,000 UI/m2), drug administration (47.5€), and hypersensitivity events management (3,622€ per episode). All transitions probabilities came from published clinical trials. Subgroup analysis was performed by risk category (standard, intermediate, and high). RESULTS:  The average direct cost of pegaspargase therapy was similar to that of native asparaginase therapy (19,756€ vs 19,373€ per patient), while avoiding 75 episodes of hypersensitivity in the sample population. The difference in cost per patient was 867€. CONCLUSIONS: Treating naïve patients with ALL with pegaspargase instead of native asparaginase may lead to less hypersensitivity episodes, less administration frequency at a minimum impact in cost in Spain.