Background: In Bowen's disease (BD) there is no consensus on optimal treatment. Photodynamic therapy (PDT) is an effective non-invasive treatment modality for BD with excellent cosmetic results. Objective: This retrospective study examines whether clinical and histological features of BD impact PDT response. Methods: Patients with previously untreated BD from 2002 until 2007 were identified at the Maastricht University Medical Centre. Patients treated with PDT were included. All histological slides were re-examined. Results: During the study period 98 tumours were treated with PDT. In univariate analysis severe atypia and higher age were associated with decreased probability of clinical clearance. Higher age was also associated with an increased risk of recurrence. In multivariate analysis severe atypia remained the only independent risk factor for therapy failure. Conclusion: In patients with BD, severe atypia and higher age are associated with an increased risk of treatment failure after PDT.