<h3>Purpose/Objective(s)</h3> Immunotherapies (IT) are effective for melanoma with extracranial metastases based on multiple phase 3 clinical trials. For patients with melanoma brain metastases (MBM), however, the role of IT is less clear. We hypothesized that treatment of MBM with IT and SRS in combination results in longer survival compared to IT alone. <h3>Materials/Methods</h3> Using the National Cancer Database, we identified 775 adult patients diagnosed with MBM between 2010 and 2017 treated with IT. We excluded those who received whole-brain radiotherapy, had a history of prior cancer, or had incomplete records. We then compared receipt of both IT and SRS (IT/SRS) vs. IT alone (IT/noSRS). Cohort assignments were based only on therapies received during the patient's first course of treatment. Our primary endpoint was overall survival (OS)—the number of days between diagnosis of MBM and last follow up or death. As a subset analysis on the IT/SRS cohort, we assessed the association between the relative timing of therapies and OS. This involved multiple statistical analyses using different definitions for relative timing: days from start of SRS to IT, proximity of therapies (IT started ≤ 28 vs. > 28 days from SRS), and sequence of therapies (IT started after vs. before SRS). Adjusted hazard ratios (aHR) were calculated using multivariable Cox regression modeling and reported with 95% confidence intervals (CI). <h3>Results</h3> Of the 775 adult patients with MBM treated with IT, 546 (70.5%) were male, 759 (98.3%) were white, and 654 (84.4%) were diagnosed in 2014-2017. Those with lung, liver, and bone metastasis numbered 275 (56.9%), 100 (20.6%), and 84 (17.4%), respectively. 492 (63.5%) patients were treated with IT/SRS, and 283 (36.5%) received IT/noSRS. The median OS was 29.5 months (95% CI: 22.3 - 44.8 mo) for IT/SRS and 11.9 months (95% CI: 9.2 - 17.2 mo) for IT/noSRS with an aHR of 0.70 (95% CI: 0.56-0.88, p < 0.01). Six-month survival probability was 83.1% (95% CI: 79.5-86.1%) for IT/SRS and 68.4% (95% CI: 62.6-73.5%) for IT/noSRS. For the IT/SRS cohort, there was no significant association between the relative timing of therapies and OS using any of the following definitions of relative timing: days from start of SRS to IT (aHR: 1.001, 95% CI: 0.998-1.004, p = 0.47), IT started ≤ 28 vs. > 28 days from SRS (aHR: 0.99, 95% CI: 0.73-1.35, p = 0.94), and IT started after vs. before SRS (aHR: 1.03, 95% CI: 0.74-1.43, p = 0.88). <h3>Conclusion</h3> Patients with MBM treated with both IT and SRS appear to have longer survival compared to IT without intracranial radiation, and the relative timing of IT and SRS does not seem to impact survival. This study is limited by a lack of records in the NCDB regarding patient performance status and radiographic characteristics, which may influence treatment decisions. These findings can guide practice while results from randomized trials (e.g., ABC-X Study, ClinicalTrials.gov, NCT03340129) are not available.