To evaluate the efficacy and safety of extended immunotherapy in first-line immune checkpoint inhibitors (ICIs)-tyrosine kinase inhibitors (TKIs) combination treatment for advanced renal cell carcinoma (RCC).We retrospectively analyzed data from patients with advanced RCC who received first-line ICIs-TKIs combination treatment at West China Hospital of Sichuan University between October 2018 and July 2024. Patients who are assessed as having a disease control status after 2 years of continuous treatment will continue to receive immune checkpoint inhibitors until the inhibitors are discontinued due to disease progression or death.A total of 86 patients were screened and 14 patients diagnosed with clear cell RCC (ccRCC) were enrolled. After 65 months of follow-up, three-year progression-free survival (PFS) rate was 71.4% and 4 year PFS rate was 59.5%. The 5 year overall survival (OS) rate was 58.3%. During extended treatment, one patient (7.1%) experienced a transition from stable disease (SD) to partial response (PR) and two patients (14.3%) experienced a transition from PR to complete response (CR). The best tumor shrinkage rates presenting after 24 months had longer PFS and OS compared to those presenting within 24 months (median PFS: not reached vs. 36 months; Hazard Ratio (HR) = 0.10, 95% CI 0.01-0.80, P = 0.03). For safety, extended immunotherapy did not increase treatment-related toxicities compared to safety profile before 24 months.Our analysis of real-world data indicates that patients with extended immunotherapy after 24 months had potential survival benefits and manageable toxicity. Large-scale, prospective studies are still needed to further verify the conclusion.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.