Simple Summary New cancer treatments have prolonged the lives for patients with metastatic melanoma in clinical trials. However, patients in clinical trials often presents with a better prognosis than other patients. It is therefore important to examine the effect of the new treatments in a real-life setting. We found that survival for patients with metastatic melanoma in a nation-wide setting were prolonged and a higher proportion of these patients were alive and without active disease 3 years after they started treatment. Abstract Approval of immune checkpoint-inhibitors (ICIs) and BRAF-inhibitors has revolutionized the treatment of metastatic melanoma. Although these drugs have improved overall survival (OS) in clinical trials, real-world evidence for improved long-term survival is still scarce. Clinical data were extracted from the Danish Metastatic Melanoma database. This nation-wide cohort contains data on all patients who received systemic treatment for metastatic melanoma between 2008 and 2016. Ipilimumab, the first approved ICI, was implemented as standard-of-care in Denmark in 2012. Hence, patients were divided in a pre-ICI (2008–2011) and an ICI (2012–2016) era. Patients were defined as long-term survivors if they were alive 3 years after initiation of systemic therapy. Data from 1754 patients were retrieved. Patients treated in the ICI era had an improved median OS (11.3 months, 95% confidence interval (CI) 10.3–12.3) compared with those in the pre-ICI era (median OS 8.3 months, 95% CI 7.4–9.5, p < 0.0001). A higher proportion of long-term survivors was observed in the ICI era (survivors >3 years increased from 13% to 26% and survivors >5 years increased from 9% to 21%; both p < 0.0001). For long-term survivors, known prognostic factors were equally distributed between the two periods, except that long-term survivors in the pre-ICI era were younger. For long-term survivors, 70% were without progression in the ICI era compared with 43% in the pre-ICI era ( p < 0.0001). For all patients, the proportion without progression increased from 5% to 18% between the pre-ICI and the ICI era ( p < 0.0001), respectively. Implementation of ICI has led to a significant increase in progression-free, long-term survival for real-life patients with metastatic melanoma.