The recent introduction of adjuvant treatments for melanoma patients impacts both patient outcomes and the costs for the National Health Service, given the previous standard of care was routine surveillance (RS). We compared the cost-effectiveness and relapse-reduction benefit of adjuvant PD-1 inhibitor nivolumab versus RS. A state-transition cost-effectiveness model was developed to compare nivolumab with RS for melanoma patients with lymph node involvement or metastatic disease after complete resection, subsequently used within the UK appraisal process. Recurrence-free survival (RFS) was estimated based on a patient-level meta-regression of the Phase III trial CheckMate 238, which compared nivolumab with ipilimumab, and CA184-029, which compared ipilimumab with placebo. Post relapse survival was estimated from weighted metastatic melanoma survival from the literature and loco-regional survival from CA184-029. The model considered a 60 year life-time horizon and included drug, administration, disease monitoring, adverse event, subsequent treatment and terminal care costs. The model structure enabled extensive testing of uncertainty including the impact of immunotherapy re-treatment. Quality of life inputs were based on EQ-5D utility data collected in CheckMate 238. The main cost driver was adjuvant treatment, however, adjuvant treatments reduced downstream costs of monitoring, subsequent therapy and terminal care as a result of improved RFS. Nivolumab resulted in an overall cost difference of £32,624 versus RS and an improved quality-adjusted life year gain (QALY) of 1.81 over a patient’s lifetime. This resulted in an incremental cost-effectiveness ratio (ICER) of £18,018 per QALY gained. Despite the limitations of Markov modelling, the model structure allowed for a full exploration of uncertainty around key clinical parameters demonstrating that adjuvant nivolumab is a highly cost-effective treatment option resulting in fewer relapses, predicted increased OS and reduced downstream treatment costs versus RS.