Background: Historically, the prognosis of advanced melanoma has been poor. Recent landmark studies (KEYNOTE-006, CheckMate 066, CheckMate 037 and CheckMate 067) have shown significant improvement in outcomes of patients with advanced melanoma treated with ICIs. In a single institution retrospective study, we evaluated the efficacy and toxicities of ICIs in patients with advanced melanoma treated in real-world clinical practice. Methods: We included patients who received pembrolizumab (PEMBRO), nivolumab (NIVO), or ipilimumab plus nivolumab (IPI/NIVO) at the University of Rochester Medical Center from June 2015 to December 2018. Patient- and cancer-related characteristics were collected and compared between treatment groups. Outcomes including duration of treatment, response rates, and adverse events (AEs) were captured. Progression free survival (PFS) and overall survival (OS) were summarized using the Kaplan-Meier method. Results: We included 89 patients (55 received PEMBRO, 20 received NIVO, and 14 received IPI/NIVO); median age at ICI initiation was 68 years (range, 28-92) and 29% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥2. Forty-five patients (51%) had ≥2 co-morbidities. Nine patients (10%) had autoimmune diseases prior to initiating ICIs and 34 patients (38%) had brain metastasis. ICIs were given as first line in 71 patients (80%). Compared to those who received PEMBRO or NIVO, patients who received IPI/NIVO were younger (median age was 61 vs.71 vs. 70, p=0.003) and had better ECOG PS (ECOG PS ≥2 was 0% vs. 40% vs. 33%, p=0.007). Table shows the outcomes for the three groups. Conclusions: Patients with advanced melanoma treated with ICIs derived similar response rates to those seen in published landmark studies. However, median OS was shorter (range was 38 months to not reached in published studies).