321 Background: Immune checkpoint inhibitors (ICIs) started a new era in the treatment of metastatic renal cell carcinoma (mRCC). CheckMate-025 and CheckMate-214 trials established the effect of ICIs in the second-line and upfront therapy of mRCC, respectively. This study aimed to share a real-life experience regarding nivolumab in the second-line treatment and beyond in mRCC Methods: We retrospectively searched the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database, which is the multicenter registry system, and extracted patients treated with nivolumab in the second line and beyond. The patients treated with nivolumab plus targeted therapy or ipilimumab were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were response rates and safety. Results: A total of 134 patients were included in this study. The median age at the starting of nivolumab treatment was 61 years (Inter Quartile Range (IQR):55-67). Three out of four patients were male. One hundred four patients (78%) had previous nephrectomy. The majority of patients had clear-cell pathology (83%). Thirteen patients (10%) had sarcomatoid features. According to International Metastatic RCC Database Consortium (IMDC) risk score, seventy patients (52%) were in the intermediate and poor prognostic group. The previous drugs administered in each line before nivolumab are shown in the table below. The number of patients treated with nivolumab was 63(47%), 45(33%), 17(13%), and 9(7%) in the second-, third-, fourth-, and fifth-line setting, respectively. The median OS was 34 months (95% Confidence Interval (CI): 24.1-43.8)) with the 15 months (IQR:5-26) median follow-up. Objective response rate (ORR) and disease control rate (DCR) was 33% and 57%, respectively. The most common grade 3 or higher AEs leading to treatment discontinuation were pneumonitis (%1.4) and colitis (<%1). Conclusions: In compliance with the CheckMate-025 trial results, nivolumab improved OS for mRCC patients treated in the second line and beyond. The median OS was slightly higher in our study than the CheckMate-025 (34 months versus 25.8 months). It may be associated with the patient population in our study. Patients up to the fifth-line setting of mRCC treatment were included in this study. Of note, there was no additional safety concern for nivolumab. [Table: see text]