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Background. The implementation of tyrosine kinase inhibitors into clinical practice improved treatment outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Lenvatinib is recommended as a first-line drug for these patients. The study objective is to analyze clinical experience with lenvatinib in patients with RR-DTC in the Russian Federation. Materials and methods. The data from 18 clinical sites in Russia was analyzed for the period December 2015 and September 2019. Seventyseven patients with histologically verified DTC, proven resistance to radioactive iodine therapy, and tumor progression (according to the Response Evaluation Criteria In Solid Tumors 1.1 criteria) were included in the study. Results.Median progression-free survival in patients included into analysis (n = 72) was 26.1 months. In patients who responded to therapy (including those with partial and complete response), median progression-free survival reached 36.2 months, which is higher than that reported in the updated results of the SELECT study (33.1 months). Lenvatinib-associated adverse events (AEs) were observed in 87 % of patients. Severe AEs were registered in 18.2 % of participants. In 6.5 % of cases, AEs lead to lenvatinib cessation; in 74 % of cases, AEs required dose reduction.Conclusion. Our findings suggest high efficacy and good tolerability of lenvatinib in patients with RR-DTC in routine clinical practice in the Russian Federation.