Background. Late progression of renal cell carcinoma (RCC) after radical nephrectomy is not uncommon, but data on systemic therapy response are limited. Aim. To analyze survival rates and responses to systemic therapy, and to identify prognostic factors in RCC patients with late progression after radical nephrectomy. Materials and methods. A retrospective analysis of data of 161 patients treated at the Municipal Oncologic Hospital No. 62 in Moscow and the Municipal Oncologic Dispensary in Saint Petersburg between 2006 and 2022 was performed. Mean patient age was 63.3 years (40–77 years), 68.1 % were men, all patients had previously undergone radical nephrectomy. 77 % of patients had a favorable prognosis and 18 % had an intermediate prognosis according to IMDC (International Metastatic RCC Database Consortium). We analyzed clinical and morphological data of patients who received systemic therapy for RCC diagnosed more than 5 years after radical nephrectomy. Statistical analysis was performed using Statistica 10.0 software packages (StatSoft, USA) by constructing Kaplan–Meier curves and survival tables, building a mathematical model of survival. Results and conclusion. Median overall survival (OS) in the overall patient cohort was 52.3 months (confidence interval (CI) 43.8–62.9), and 3-year and 5-year OS were 64 % (95 % CI 57–72) and 43 % (95 % CI 36–52). All patients received first-line targeted therapy: tyrosine kinase inhibitor therapy was administered to 159 (98.7 %) and mTOR inhibitor therapy to 2 (1.3 %) patients, respectively. Median duration of first-line therapy was 34.1 months; 124 (77 %) patients received second-line therapy. Univariate analysis in patients with late RCC progression showed that histologic variant (p = 0.048) and degree of tumor differentiation (p = 0.005), number of metastases (p = 0.003), metastases to lymph nodes (p = 0.026) and performance of metastasectomy (p = 0.028) were additional factors independently affecting OS rates. Multivariate analysis showed that histological variant (p = 0.048) and degree of tumor differentiation (p = 0.045), IMDC prognosis (p = 0.005), bone metastases (p = 0.039), brain metastases (p