Introduction. There are several forms of the L-asparaginase which are characterized by differences in the half-life, the spectrum of toxicity as well as other factors.Aim — to determine the incidence of different types of L-asparaginase toxicity in adult patients with Ph-negative acute lymphoblastic leukemia (ALL) treated according to the ALL-2016 protocol.Materials and methods. From December 2016 to February 2023 the multicenter prospective randomized study “ALL-2016” included 313 patients with newly diagnosed Ph-negative ALL. Information about the 256 patients who had toxicity of native L-asparaginase was entered into an electronic database. The ratio of men and women was 155:101. The median age was 32 (18–54) years. We analyzed 1253 courses of therapy that included the administration of L-asparaginase.Results. L-asparaginase toxicity and adverse reactions were diagnosed in 67 (26 %) of 256 patients. Of the 1253 courses, 102 (8 %) had complications associated with the administration of this drug. Grade 1–2 toxicity of L-asparaginase was diagnosed in 34 (51 %) patients: allergic reaction — in 6 (18 %), thrombosis of brachiocephalic veins associated with the installation of a central venous catheter — in 2 (6 %), increased pancreatic amylase in blood serum and diastase in urine, without clinical signs of pancreatitis — in 3 (9 %), lower protein-synthesis function of liver — in 23 (68 %), hepatotoxicity — in 15 (44 %). Grade 3–4 toxicity of L-asparaginase was diagnosed in 33 (49 %) patients, of which 22 (67 %) required discontinuation of the drug. The median of the development of complications of L-asparaginase was the third administration. None of the patients died as the result of the toxicity of native form of the drug. The 5-year overall survival (OS) and the probability of relapse (PR) in the group of patients in which L-asparaginase was discontinued at the stage of induction of remission and in the group of patients who continued L-asparaginase treatment at remission consolidation and maintenance therapy did not differ significantly: OS — 89 % vs 70 % (p = 0.0921), PR — 47 % vs 33 % (р = 0.8633).Conclusion. In adult patients, L-asparaginase withdrawal due to toxicity, in most cases, occurs at the stage of the remission induction. It is possible that the replacement of the native form the drug to the pegylated one in adult patients with ALL, in whom L-asparaginase is canceled at the stage of remission induction, improves long-term survival rates.