Background: The treatment landscape of advanced Renal Cell Carcinoma (aRCC) has changed over the last years with the incorporation of immune checkpoint blockers (IO) to tyrosine kinase inhibitors (TKI). Today there are available several options based on the combination of IO-IO and IO-TKI in the first line setting for advanced disease (R. J. Motzer et al. (2018); Rini et al. (2019); Choueiri et al. (2021) R. Motzer et al. (2021)). Herein we present an observational retrospective study of patients treated with a combo in the clinical practice in Spain. Purpose: Main Objective: To describe the survival outcomes of patients diagnosed with aRCC treated in the context of routine clinical practice in our center. Secondary Objectives: (1) To explore other efficacy endpoints of IO-IO or IO-TKI in the first line, (2) to compare efficacy endpoints and safety profile of IO-IO versus IO-TKI and (3) to describe the safety profile of combos. Methods: We enrolled 53 patients between February 12, 2019 and January 12, 2023 in the University Clinical Hospital of Santiago de Compostela. All patients signed an informed consent before enrolling in the study. Results: With a median follow-up of 11.93 months, median overall survival was not reached. We observed a median progression free survival (PFS) of 10 months, (95% CI 6.8-NA). Nine patients were treated with Cabozantinib-Nivolumab, 10 patients with Axitinib-Pembrolizumab, 33 patients with Ipilimumab-Nivolumab (IO-IO) and 1 with Lenvatinib-Pembrolizumab. All (12 patients) IMDC good risk patients were treated with IO-TKI combo, meanwhile intermediate and poor risk patients received IO-TKI (8 cases) and IO-IO (33 patients). Patterns of treatment response were as follow (% complete responses / % partial responses): IO-TKI 15/55%, IO-IO 6.5/26%. Eleven (55%) and 15 patients (47%) received a nephrectomy in IO-TKI and IO-IO groups, respectively. Regarding tumor histology, only 2 were non-clear cell carcinomas, both with a papillary histology. In the intermediate-poor risk groups there was a non statistically significant trend towards a better overall survival favoring IO-TKI regimens (HR 1.84, 95% CI 0.65 - 5.20). Reported grade 3-4 adverse events were as follow: in IO-TKI group diarrhea (11%), hepatitis (11%) and bowel perforation (1 case); in IO-IO group were nephritis (11%), pneumonitis (11%), 1 case of tumor lysis syndrome and one of myocarditis. Conclusions: Combos of IO-IO & IO-TKI have increased overall response rate and survival in patients with aRCC. There are no statistically significant OS differences between IO-IO & IO-TKI. Immediate or delayed nephrectomy seem safe in selected patients. Together with clinical aspects, clinical trial availability & drug regulatory status determine the selection of combination therapies.