Pembrolizumab is an anti-programmed cell death-1 monoclonal antibody, currently representing the first-line treatment for advanced melanoma. Apart from registration trials, there is a paucity of data on its effectiveness and safety in a real-world setting. We retrospectively analyzed patients with metastatic melanoma treated at our institution in the context of an Expanded Access Program. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Overall, 42 melanoma patients were treated. BRAF status was wild type in 30 (71%) patients and mutated in 12 (29%). Twelve (29%) patients received pembrolizumab as the II line treatment, the other 30 (71%) as at least III line treatment. One (2%) patient experienced complete response, six (14%) partial response, and seven (17%) stable disease; 39 (93%) patients had disease progression. Median progression-free survival and overall survival were 2.4 (range: 0.2-46.5) and 5.5 months (range: 0.2-47.1), respectively. Results of the multivariate analysis showed that performance status [hazard ratio (HR): 7.10; 95% confidence interval (CI): 2.73-18.4; P<0.001] and the number of previous therapeutic lines (HR: 1.84; 95% CI: 1.08-3.13; P=0.025) influenced progression-free survival. Similarly, performance status (HR: 6.14; 95% CI: 2.44-15.4; P<0.001) and the number of previous lines (HR: 2.04; 95% CI: 1.17-3.56; P=0.012) influenced overall survival. Fourteen (33%) patients reported immune-related adverse events. Three (7%) patients discontinued treatment due to immune-related adverse events onset. At present eight (19%) patients are still alive and one patient is still on treatment. Despite the limitations related to the size and characteristics of this report, our experience confirms the use of pembrolizumab for advanced melanoma in a real-life setting.