Background: The majority of data for IO in melanoma stems from trials that have specific inclusion criteria and often exclude important populations. In this analysis, we present the first real-world evidence of outcomes for stage IV patients (pts) with cutaneous melanoma receiving IO from 2015–2017 (addition of anti-PD-1 therapies) and factors associated with receipt of IO, and compare these outcomes with pts receiving IO (likely interferon and interleukin-2) from 2004–2010, and IO (addition of ipilimumab) from 2011–2014. Methods: The NCDB was analyzed to identify pts with stage IV melanoma from 2004–2017. Pts were categorized into receipt of IO or not during time periods 2004–2010, 2011–2014, and 2015–2017. Overall survival (OS) was analyzed by Kaplan-Meier, log-rank, and Cox proportional hazard models; IO status was analyzed using logistic regression. Results: 24,544 pts were analyzed from 2004–2017. Overall, 5,238 pts (21.3%) that received IO had improved median OS compared to those that did not (20.2 vs. 7.4 mos; p<0.0001). 4.1% received IO from 2004-2010, 7.8% from 2011-2014, and 9.4% from 2015-2017. Three-year OS significantly improved in pts treated with IO across treatment years; p<0.0001 (Table). Similarly, median time to IO initiation improved over time: 62 days in 2011-2014 vs. 49 days in 2015-2017 (p<0.0001). In the overall cohort, age<65 years, female gender, private insurance, no comorbidities, residence in metropolitan area, and treatment at academic centers were associated with better OS (p<0.0001 for all). Race was not associated with differences in OS (p=0.07). Multivariate analysis for 2015-2017 demonstrated that lack of treatment with IO [HR 1.98, 95%CI 1.81-2.17], radiation therapy [HR 1.20, 95%CI 1.09-1.32], presence of liver metastases [HR 1.87, 95%CI 1.63-2.13], and lack of surgery [HR 1.68, 95%CI 1.45-1.93] were independently associated with worse OS (p<0.0001 for all). In multivariate analysis, receipt of IO from 2015-2017, was associated with age<65 years [OR 1.27, 95%CI 1.08-1.50], African American race [OR 5.88, 95%CI 1.60-28.58], lack of comorbidities [OR 1.43, 95%CI 1.23-1.66], and treatment at academic centers [OR 1.44, 95%CI 1.26-1.65] (p<0.05 for all). Conclusions: OS was improved in stage IV melanoma pts receiving IO, with the highest OS rate in 2015-2017. Our findings that represent a real-world population are consistent with recent trials, like KEYNOTE 006 and CheckMate 067 where 3-year OS for anti-PD-1 therapy was 50% and 52%, respectively. In our study, African Americans demonstrate a 5-fold increase in likelihood of receiving IO, a population underrepresented in clinical trials. Significant socioeconomic factors may impact receipt of IO and survival.