Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy in the case of complete response on metastatic sites is still unknown. We aimed to evaluate the feasibility of nephrectomy for residual disease in patients with metastatic renal cell carcinoma (mRCC) and complete response (CR) on metastatic sites following ICI. Methods: Patients who underwent partial or radical nephrectomy after prior ICI between 2015 and 2018 were retrospectively included and clinicopathological data were reviewed. Perioperative data and postoperative outcomes were recorded. Results: Eleven patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of complete response on metastatic sites. Median age was 59.8 years [38-67]. All patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (81.8%) or poor (18.2%). ICI was administered as first-line therapy in 36.4% of cases (4/11) and as second-line option after TKI in 63.6% of cases (7/11). Treatments regimens were: nivolumab + ipilimumab (n = 3), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 6). The median duration of ICI treatment was 10 months (range: 3-38 months) and the mean number of cycles was 27 (range: 6-75). Median operative time was 243 minutes [135-345] and mean blood loss was 909 cc [40-4000]. In 81.8% (n = 9) of the cases, surgeons experienced challenges for finding dissection planes due to inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 54.6%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 54.6% and complete pathological response in 2 cases. Median follow-up was 15 months, with 73% of patients free from progression and 54% free from systemic treatment at 1 year. Conclusions: Nephrectomy following ICI for mRCC could allow achieving CR in selected patients. Due to technically complexity and complications rates, this surgery should be performed in centers with extensive experience.