Background: Patients (Pts) with metastatic melanoma presenting with brain metastases (MBM) have a high morbidity and mortality risk. The combination of ipilimumab/nivolumab (I/N) has demonstrated high intracranial response rates in selected, asymptomatic pts, suggesting there is a subset of pts who may be able to forgo or delay intracranial therapies. There is currently limited real world data on how many pts with MBM are successfully treated with this approach. We sought to explore our clinical experience at Duke University with combination immune checkpoint inhibitors for pts with MBM. Methods: An electronic database search was conducted for all metastatic melanoma pts treated with PD-1 therapies between 2015 and 2021. Pts treated with combination ICIs for brain metastases were included. The primary outcome was overall survival (OS). Secondary outcomes were need for local therapies (radiation (RT): stereotactic radiosurgery or whole brain radiation therapy or craniotomy), and immune related adverse events (irAEs). Results: Between 2015 and 2021, 66 pts with MBM received I/N, with a median follow-up of 30.4 months. Median age was 68, 60.6% were male and 61% had a BRAF mutation. 38 pts were asymptomatic. Of the 28 symptomatic patients 61% were on corticosteroids at the time of I/N initiation. 56% of pts received local therapy prior to start of I/N, 17% during and 18% after discontinuing I/N. 53% of pts were initiated on I/N as first line systemic therapy for MBM. 56% of patients had to discontinue I/N after one cycle because of high-grade irAEs. 13.8% of patients that received RT to the brain developed radionecrosis. Median OS was 25.6 months in the overall cohort, with a 1 year OS of 63%. There was a trend towards a higher risk of death for symptomatic versus asymptomatic patients HR:1.96 [95% CI: 0.96, 3.97; P:0.06]. Of the 38 asymptomatic patients, only 6 patients did not receive local therapies with either RT or craniotomy. Two of these patients died from melanoma progression, one from intra-cranial progression, the other from both intra-cranial and extra-cranial progression, and 4 remain alive without evidence of progression. Conclusions: The majority of pts with MBM are ultimately treated with multimodality therapy. Advances in systemic therapies have provided meaningful clinical benefit that could allow a limited number of asymptomatic patients to forgo local therapy, but currently few pts are treated in this manner.