OBJECTIVES: A cost-effectiveness analysis (CEA) has been performed, from an Italian public payer perspective, to compare the first advanced therapy medicinal product (ATMP) containing stem cells for the treatment of Limbal Stem Cell Deficiency (LSCD) with conservative treatment, a standard alternative pathway. LSCD is a rare condition characterized by the shortage of limbal stem cells in the eye resulting in corneal conjunctivalization, corneal opacity, visual impairment and even blindness. A medicinal product has been recently approved by EMA as the first treatment in moderate-severe LSCD due to chemical or physical burn. METHODS: Efficacy data derive from a retrospective, case-series, non-randomized, non-controlled, multicenter clinical study in which patients have been treated with ex-vivo expanded autologous human corneal epithelial cells containing stem cells. Symptoms like pain, photophobia and burning, together with visual impairment, contributed to assess quality of life associated with the condition, while Quality Adjusted Life Years (QALYs) have been used to compare the outcomes of the recent approved product with conservative management, in a comparable patient pool. The considered cost data have been obtained from Italian tariff nomenclature databases. RESULTS: Patients treated with conservative management presented QALY values between 6.51 and 9.71, depending on LSCD severity, whereas treatments with ATMP ensured to patients between 10.22 and 13.60 QALY, with a total utility gain between 3.71 and 4.60 QALYs (result being discounted by 3.5% yearly).   As a result of this utility gain, the approved product would meet an ICER threshold of 40,000 €/QALY cost of around €160,000 per treatment. CONCLUSIONS: Offering long-term, potentially life-long, effectiveness after single treatment, ATMP analyzed delivers cost reduction in the long term management of LSCD, despite higher initial costs compared to conservative approach. The CEA of the product demonstrated a significant gain in terms of QALYs, amortizing the initial outlay for the treatment.