OBJECTIVES: Metastatic melanoma has a poor prognosis with 10 year survival being <5%. Standard therapy is the effective but costly Ipilimumab. An emerging 1st line treatment is Tumor Infiltrating Lymphocytes (TIL), with response rates >50% and expected survival rates of 25%-42% versus 45% (1yr) and 23,5% (2yr) for Ipilimumab. TIL is highly personalized, however complex and requests substantial upfront investments from the hospital in expensive lab-equipment, staff expertise and training, as well as extremely tight hospital logistics. Therefore, an early health economic modelling study, supporting a Coverage with Evidence Development (CED) program, was performed. METHODS: We used a Markov decision model to estimate the expected costs and outcomes (quality adjusted life years; QALYs) for TIL versus Ipilimumab in metastatic melanoma patients from a societal perspective over a life long time horizon. Three mutually exclusive health states (stable disease, progressive disease and death) were modelled, divided in first and second line treatment. Technical failures and non-compliance were incorporated to reflect the dynamic nature of the technology. To inform further research prioritization, Value of Information (VOI) analysis was performed. RESULTS: TIL is expected to yield more QALYs compared to Ipilimumab (0.99 vs 0.52 respectively) at lower total costs (€83,588 vs €87,834 respectively). Based on current information TIL has a probability of 88% for being cost effective at a cost/QALY threshold of €30,000. Expected Value of Perfect Information (EVPI) amounted to €1,2 million. Partial EVPI (EVPPI) was highest for survival data (€550,000). Expected Value of Sample information was estimated €355,000 for an optimal sample size of n=50. CONCLUSIONS: TIL is expected to improve QALYs compared to Ipilimumab at lower incremental cost and has the highest probability of being cost-effective. To reduce decision uncertainty, a future clinical trial to investigate survival seems most valuable, and should preferably be undertaken as part of a CED program.