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Background: Actinic keratosis (AK) is a UV-induced, pre-malignant skin condition that is common in adults over 60 years of age with fair skin in Scotland. The most commonly prescribed first-line treatment for AK in Scotland is currently diclofenac gel (3 %). Ingenol mebutate gel is a recently developed topical therapy available in two strengths for the treatment of AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days)., Objective: To compare the cost-effectiveness of two strengths of ingenol mebutate gel developed to treat AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days) with other first-line AK therapies including diclofenac gel, 5-FU, 5-FU/salicylic acid, and cryotherapy for the first-line treatment of AK in adult patients, from the perspective of the National Health Service (NHS) in Scotland., Methods: A cost-utility analysis was conducted using a decision-tree approach to calculate the costs and benefits of different treatment strategies for AK on the face and scalp or trunk and limbs over a 12-month time horizon. Data on the relative efficacy of treatments were obtained from a systematic literature review and meta-analysis. Utility scores and resource-use data were obtained from published sources., Results: Over 12 months, ingenol mebutate 150 mcg/g gel and 500 mcg/g gel were cost-effective compared with the most commonly used topical therapy in Scotland, diclofenac (3 %) gel, at a willingness-to-pay threshold of £20,000 per QALY, with a minimal additional cost of £43 and £105, respectively per QALY gained., Conclusions: Ingenol mebutate gel is a cost-effective therapy for the first-line treatment of AK from a Scottish NHS perspective.