OBJECTIVES: Oral Isotretinoin (OI) is the gold standard for treating severe nodular acne but is associated with a significant adverse events burden. In the 20-week POWER trial, Adapalene 0.1% / Benzoyl Peroxide 2.5% (A/BPO), a topical fixed-dose combination treatment, plus oral antibiotic doxycycline 200mg/day (D+A/BPO) demonstrated a favourable composite efficacy/safety profile compared to OI in severe nodular acne patients. The objective of the present study was to assess the one-year cost-effectiveness of D+A/BPO versus OI. METHODS: A Markov model was developed for the Swedish setting based on clinical effectiveness data from the POWER trial and the typical treatment pathway patients experience following treatment failure, discontinuation or relapse. Patients’ acne was classified as “controlled” following at least 2-grade improvement in the Investigator’s Global Assessment. Health state utility values (HSUV) for controlled and uncontrolled acne were estimated by applying the Swedish tariff to the EuroQOL five dimensions questionnaire responses collected at baseline and study end, although the difference in the two HSUVs was minimal. Adverse events observed in the POWER study were included, with impact on costs and quality of life.  RESULTS: D+A/BPO treatment was less costly than OI at 17,033 SEK versus 21,185 SEK per patient. Costs results favoured D+A/BPO due to the lack of costs associated with monitoring when receiving OI as well as lower adverse events treatment costs, combined with lower frequency and cost of physician visits as patients treated with D+A/BPO consult a general practitioner rather than a dermatologist. The total number of Quality-Adjusted Life Years accrued over one year was comparable at 0.9250 for D+A/BPO and 0.9318 for OI. Sensitivity analyses showed that D+A/BPO was no longer less costly when increasing the associated frequency of physician visits or decreasing visits with OI. CONCLUSIONS: For severe nodular acne patients, D+A/BPO may be considered an attractive, lower-cost, first-line alternative to OI.