Background: IMAGE (ipilimumab: management of advanced melanoma in real practice) is an ongoing multinational, prospective, observational study that assesses the treatment of advanced (unresectable or metastatic) melanoma (MEL) in a real-world setting. Although there are adequate accumulating overall survival (OS) data from randomized controlled trials for patients (pts) diagnosed with advanced MEL, OS data from robust real-world studies are not available. As a result, the IMAGE study evaluated OS in pts with advanced MEL who received ipilimumab (IPI) and non-IPI therapies. Methods: IMAGE included adult pts who were not participating in a clinical trial and received IPI or other non-IPI therapies. Pts were followed from study enrollment (April 2012) to data extraction (November 27, 2015). Data were collected by electronic case report forms. Results: Of the 1,371 pts included in this study, 84% (n = 1,152) received IPI therapy and 16% (n = 219) did not receive IPI at any time during the study period. At study entry, 60% of pts were male, median age was 64 years, mean follow-up was 8 months, 79% were on second or subsequent line of systemic therapy, 97% had distant metastases, and among 94% of pts (n = 1,285) with BRAF testing, 42% (n = 540) expressed the mutation. In non-IPI pts, the most common systemic MEL therapies were dacarbazine (17%), fotemustine (17%), vemurafenib (15%), dabrafenib (13%), and pembrolizumab (9%). Median OS during the study period (study entry to death or censoring at discontinuation, study completion, or data extraction date) was 11 months (95% CI: 10–13) for IPI pts and 9 months (95% CI: 6–11) for non-IPI pts. The OS probability at year 1 was 48% (standard error: 2%) for IPI pts and 41% (standard error: 4%) for non-IPI pts. Conclusions: Although these are interim data and further follow-up analyses will be needed to confirm these findings, the OS results from IMAGE are consistent with those observed in advanced MEL clinical trials showing improved OS with IPI.