Background: Systemic immune checkpoint blockade therapy anti-PD1 nivolumab combined with anti-CTLA-4 ipilimumab is an effective therapy for metastatic melanoma. The treatment, however, has a high frequency of immune related adverse events. Interestingly, immune-related adverse events in anti-PD1 and anti-CTLA4 monotherapy have been associated with an improved overall survival in melanoma. Whether immune-related events correlate with enhanced outcomes in ipilimumab/nivolumab combination therapy is unknown. Methods: Clinical data from patients diagnosed with untreated cutaneous stage IV melanoma receiving ipilimumab/nivolumab combination therapy between 2015-2018 at the Massachusetts General Hospital (MGH) and have been analyzed retrospectively. Tumor response was measured using RECIST criteria. Primary endpoints were frequencies and characteristics of immune-related adverse events, overall survival, and response to therapy. Results: A total of 57 patients received ipilimumab/nivolumab combination therapy. During a mean follow-up period of 26 months, 28 (49%) patients completed the therapy. Immune-related adverse events were observed in 45 (79%) patients, with rash (28%), colitis (23), hepatitis (21%) and fever (21%) being the most frequent. Overall survival was 29 months in patients with immune-adverse related events and 14 months in the group without any adverse events (p-value < 0.01). The onset of hypophysitis correlated with tumor response (p = 0.02) and hepatitis showed a trend in a correlation to response of therapy (p = 0.06). Conclusions: Our study demonstrates the association between improved overall survival and the onset of immune-related adverse events in ipilimumab/nivolumab combination therapy. A trend correlated with improved outcomes and onset of immune-related adverse events was seen in hepatitis and was significantly associated with hypophysitis, however these results must be interpretated carefully as larger studies must confirm our findings. Despite small study size, we are the first to describe an association between immune-related adverse events in ipilimumab/nivolumab combination therapy.