OBJECTIVES: To estimate the incremental cost utility ratio (ICUR) for ingenol mebutate vs imiquimod 5% for actinic keratosis (AK) patient’s treatment on the face and scalp, in Spain. METHODS: A Markov model was used to simulate AK patient treatment evolution for a 5-year horizon from the Spanish National Health System (NHS). Duration of ingenol mebutate treatments was 3 days and 12 days for imiquimod 5%. Effectiveness measure was total clearance rate obtained from indirect mixed comparisons (42.24% for ingenol mebutate and 44.54% for imiquimod) and adjusted according compliance (90% for ingenol mebutate and 60% for imiquimod). Annual recurrence rate (20%) derived from literature. Annual discount rate of 3% was applied for costs and outcomes. Total cost estimation (€,2015) included: drug (retail price VAT included with mandatory deduction), and dermatology visits cost (for adverse events and disease management).Utilities values (0.986 for AK and 1 for clearance) were used to derive quality-adjusted-life years (QALY). Probabilistic and deterministic sensitivity analyses were performed to confirm the robustness of the obtained results. RESULTS: Ingenol mebutate showed higher effectiveness than imiquimod 5%, 0.535 vs 0.503 total gained clearances and 4.451 vs 4.449 total QALYs and accounted higher total costs, €551.50 (46% drug cost) versus €527.89 (36% drug cost) compared to imiquimod 5%. Estimated ICUR was €10.906/QALY gained with ingenol mebutate vs imiquimod 5%. In probabilistic sensitivity analysis performed, 78% of simulations yielded an ICUR below €30,000/QALY for ingenol mebutate versus imiquimod. CONCLUSIONS: Ingenol mebutato vs imiquimod 5% was an efficient alternative for NHS for patients with AK, on face and scalp, considering an acceptable threshold of €30,000/QALY.