BackgroundClinical trials have demonstrated promising outcomes for adjuvant immunotherapy in patients with resected melanoma. Real-life data provide valuable insights to support patient guidance and treatment decisions. MethodsObservational population-based study examining a national cohort of patients with resected stage III-IV melanoma referred for adjuvant therapy. Data were extracted from the Danish Metastatic Melanoma Database (DAMMED). ResultsBetween November 2018 and January 2022, 785 patients received adjuvant anti-PD-1. The majority had stage III resected melanoma (87%), normal LDH levels (80%), and performance score 0 (87%). Patients were followed for a median of 25.6 months (95%CI 24−28). The median recurrence-free survival (RFS) and melanoma-specific survival (MSS) were not reached. The RFS was 78% (95%CI 75−81), 66% (63−70), and 59% (55−63); MSS was 97% (95−98), 93% (91−95), and 87% (84−90) at 1-, 2-, and 3-year; respectively. Less than half (42%) of the patients finalized planned therapy, 32% discontinued due to toxicity, and 19% due to melanoma recurrence. Patients discontinuing adjuvant treatment prematurely, without recurrence, had similar outcomes as patients finalizing therapy. In a multivariable analysis, ipilimumab plus nivolumab did not improve outcomes compared to ipilimumab monotherapy as a first-line metastatic treatment after adjuvant anti-PD-1. ConclusionSurvival outcomes in real-world patients with melanoma treated with adjuvant anti-PD-1 align with results from the randomized controlled trials. Patients discontinuing therapy prematurely, for other reasons than recurrence, had similar outcomes as patients finalizing planned treatment. First-line metastatic treatment with ipilimumab and nivolumab post-adjuvant anti-PD-1 did not show improved outcomes compared to ipilimumab/anti-PD-1 monotherapy.