Data regarding the efficacy and safety profiles of immune checkpoint inhibitors (ICIs) for metastatic renal cell carcinoma (mRCC) trial-ineligible patients in the real world remain unclear. The aim of this study was to clarify the impact of trial eligibility on ICI-based combination therapy for mRCC. We collected clinical data of mRCC patients receiving ICIs since 2016, and 222 patients were registered. Among these patients, we evaluated 93 patients treated with ICI-based combination therapy, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, or avelumab plus axitinib, as first-line therapy. Patients were classified into the trial-ineligible group when they had at least one of the following factors at the time of treatment initiation: Karnofsky performance status (KPS) <70%, hemoglobin level <9.0g/dL, estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2, platelet count <100,000/µL, neutrophil count <1500/µL, non-clear cell histology, or brain metastasis. The remaining patients were classified into the trial-eligible group. Forty-eight patients (52%) were classified into the trial-ineligible group. The frequency of patients with trial-ineligible factors was highest for low eGFR (n=20, 45%), followed by non-clear cell histology (n=17, 36%) and low KPS score (n=12, 25%). There was no significant difference in progression-free survival (median: 24.0 vs. 11.0 months, p=0.416), overall survival (1-year rate: 87.0% vs. 85.3%, p=0.634), or objective response rate (52% vs. 42%, p=0.308) between the trial-eligible and -ineligible patients. The incidence rate of adverse events was higher in the trial-eligible patients than in the trial-ineligible patients (91% vs. 75%, p=0.0397); however, the rate of grade 3 or higher adverse events was comparable between the two groups (42% vs. 40%, p=0.796). There are many trial-ineligible patients in the real world. Nevertheless, the efficacy and safety of ICI-based combination therapy in trial-ineligible patients were non-inferior compared with those of trial-eligible patients.