Introduction. Methotrexate (MTX) is one of the most commonly used anti-tumor preparations which confirm it effectiveness against the large spectrum of the oncological diseases in children. Today the use of high doses of the MTX (g/m2 ) in the monotherapy or in combination with other chemotherapeutic agent is a standard of treatment of such nosology as osteosarcoma, tumors of the central nervous system (CNS), lymphomas, acute lymphoblastic leukemia. Despite of the developed recommendations on the fluid therapy, therapeutic monitoring, use of leukovorin which allowed to reduce the expected toxicity among some patients it is not always possible to prevent the development of complications. Ex post evaluation of different doses of schedule of the high-dose MTX is necessary in order to formulate new and effective treatment strategies with respect to the individual specifics of the patients. Materials and methods . During the period from October 2015 to February 2018, a patient cohort (n = 26) who received high-dose MTX therapy with the following nosology: osteosarcoma – 4, hemoblastosis – 11, and CNS – 11 tumors was evaluated. The average age of the patients was 7.3 years old; ratio of boys:girls – 2.25: 1. The used doses were ranged from 1 to 12 g/m 2 , the doses schedules ranged from 4 to 36 hours; the total number of courses during the observation period was 94; the average number of courses per patient was 3. In all cases, the level of MTX in the blood serum was monitored with correction of the dose of leucovorin according to international recommendations. Estimated toxicity parameters were the following: allergic reactions, skin and mucous membrane damage, neurologic disorders, myelosuppression, hepatic transaminase and creatinine growth. Results. Transitory toxicity was noted for 100 % of patients, of which clinically significant was in 62.7 % of cases. The development of complications that had required the use of antibacterial and blood transfusion therapy occurred after 36 courses of therapy (38.2 %), of wich in 24 cases (66.6 %) MTX was performed in combination with other antitumor agents. No cases of acute kidney injury were presented, there was no significant difference in creatinine level before and after high-dose MTX courses. The highest frequency of episodes of hepatotoxicity was noted in the group of patients diagnosed with “osteosarcoma”. After reduction the episodes of toxicity with the use of high-dose MTX, all patients continued programmed chemotherapy. Conclusions. Against the background of an adequate accompanying therapy (infusion therapy with alkalization of urine, pharmacodynamic monitoring, correction of the leucovorin dose), it is possible to achieve satisfactory tolerability of high doses of MTX. The combination of high doses of MTX with other antitumor drugs leads to a significant increase in the toxicity. Despite of the noted complications of therapy, continuation of treatment with the use of previous doses of MTX (does not require reduction) is possible, and a decrease in the rate of MTX removal is not always a predictor of episodes of the toxicity.