OBJECTIVES: Methyl aminolevulinate cream is the first licensed topical PDT product in the UK to treat actinic keratoses (AK). It is activated when the cream is illuminated with a red light source (MAL-PDT). In the UK, the incidence rate of AK is 5%. The aim of this study was to assess the cost-effectiveness of MAL-PDT versus the most commonly used intervention, cryotherapy. METHODS: Clinical outcomes were obtained from a multicentre comparative trial of difficult to treat AK (Foley et al. Journal of Dermatol Treat (2003)), defined as thin or non-hyperkeratotic AK on the face or scalp. Resource use was from a Delphi panel of dermatologists and costs from standard UK sources. The NHS perspective was taken and included direct costs only. In the decision analytical model, patients either receive MAL-PDT or cryotherapy first line with second line therapy depending on lesion response. A one-year time horizon was used to capture all relevant resource use and to assess the clinical response. An excellent cosmetic outcome was defined as 100% complete lesion response, but also no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared to adjacent skin. Key efficacy data from the clinical trial were subjected to a stochastic sensitivity analysis using a Beta prior distribution and 1000 simulations. RESULTS: From the deterministic model, the MAL-PDT strategy dominated cryotherapy. Seventy-three percent of patients had an excellent cosmetic outcome with MAL-PDT at a cost of £832.93 per patient compared to 42% of cryotherapy patients (£843.08 per patient). In the stochastic analysis using 1,000 simulations, 95% of the ICERs were in the range -£161 to £191. MAL-PDT was the dominant in strategy in 66.3% of the simulations. CONCLUSIONS: MAL-PDT is at least as cost-effective as cryotherapy in the treatment of thin or non-hyperkeratotic actinic keratoses (AK) on the face or scalp and has superior cosmetic outcomes.