OBJECTIVES: Actinic keratosis (AK) caused by chronic exposure to ultraviolet radiation, is the most common premalignant dermatological disease in adults over 60. Topical field treatments are effective in clinical and subclinical lesions. There are currently three topical treatment options available in Greece: diclofenac gel (3%), imiquimod (5%) and a recently launched agent: Ingenol mebutate gel (IM). The objective of the present study was to perform a cost-effectiveness analysis of IM vs other topical alternatives for the treatment of AK from a Greek healthcare perspective. METHODS: The analysis was conducted via a decision tree in order to calculate the clinical effects and associated costs of AK first-line treatments: IM (2-3 days), diclofenac (3% for 8 or 12 weeks) and imiquimod (5% for 4 or 8 weeks), over a 24-month horizon, divided in 6-month cycles, by considering a hypothetical cohort of immunocompetent adult patients with clinically confirmed AK on the face/scalp or trunk/extremities. Clinical data on the relative efficacy of the different strategies under consideration were obtained from a network meta-analysis, while inputs concerning resource use, reflecting the clinical practice derived from an expert panel. All costs were calculated from a Greek third-party payer perspective. RESULTS: IM 0.015% and 0.05% were both cost-effective compared to diclofenac and below a willingness- to-pay threshold of 30,000€/QALY (7.857, and 4.451 €/QALY gained for IM 0.015% compared to diclofenac 2xdaily for 8 and 12 weeks respectively). Comparing IM on face/scalp AK lesions for 3 days versus imiquimod (4 or 8 weeks) resulted in equivalent results (22.964€ and 787€/QALY gained) while IM use on trunk/extremities was dominant compared to imiquimod four weeks treatment. CONCLUSIONS: From a social insurance perspective in Greece, IM 0.015% and IM 0.05% could be the most cost-effective first-line topical filed treatment options in all cases for the treatment of Actinic Keratosis.