Background: Biomarkers to select mRCC patients most likely to benefit to immunotherapy are needed. The retrospective multicentre Meet-URO-15 study evaluated the prognostic role of peripheral blood cells in mRCC patients treated with Nivolumab. Methods: Complete blood count was assessed at the first four cycles of Nivolumab. The primary endpoint was median overall survival (mOS) according to bNLR. NLR was defined as neutrophil / lymphocyte (cutoff = 3) and ΔNLR the difference between NLR at 2^nd cycle and bNLR (median as cutoff = 1.1). Results: From October 2015 to October 2019, 470 patients started Nivolumab as 2^nd (67%), 3^rd (22%) and > 3^rd (11%) line. Median age was 66 years, 71% were male and 83% had clear cell histology. Baseline IMDC group was favorable in 25%, intermediate in 63% and poor in 12%. Lymph-nodes, visceral and bone metastases were present in 54%, 91% and 36%. mOS and progression-free survival (PFS) were 34.8 and 7.5 months. Overall response rate (ORR) and disease control rate (DCR) were 30% and 61%. bNLR was available in 404 patients: bNLR < 3 (54%) correlated with statistically significant longer PFS [11.4 vs 5.4 months; HR 1.69 (1.33-2.15)] and OS [46.2 vs 17.2 months; HR 2.37 (1.72-3.26)] (both p< 0.001), with similar ORR (35% vs 30%, p= 0.28) but higher DCR (71% vs 52%, p< 0.001). ΔNLR was available in 360 patients: ΔNLR < 1.1 (73%) correlated with a statistically significant improvement of PFS [11.2 vs 4.9 months; HR 1.53 (1.16-2.03), p= 0.03], OS [Not Reached vs 19.7 months; HR 1.83 (1.28-2.61), p= 0.001], ORR (37% vs 23%, p= 0.011) and DCR (68% vs 53%, p= 0.008). Multivariate analyses adjusted for IMDC group, line of therapy and metastatic sites, confirmed the statistically significant correlation of bNLR and ΔNLR with OS, PFS and DCR. Conclusions: Our study showed the statistically significant correlation of lower bNLR and early ΔNLR with longer OS, PFS and higher DCR in mRCC patients treated with Nivolumab.