Background: Oral psoralen-ultraviolet A (PUVA) has been the treatment of choice of moderate to severe forms of psoriasis, however there is no standardized worldwide protocol. Twice- and thrice-weekly regimens had been used. In this study we compare the efficacy of these regimens. Methods: Two PUVA regimens in 28 patients with clinical diagnosis of psoriasis, with symmetric and no less than 20% of body surface area involvement, using a half-body study, were compared. Each patient body half was randomized to receive either twice- or thrice-weekly PUVA. A blinded trained dermatologist assessed the PASI score in each body half at the beginning of the study and at clearance or after 25 sessions. Results: Twenty-three patients completed the study. There were no significant differences in the efficacy of both treatments considering the median percentage of PASI decrease (92.9% for the body half with the twice-weekly regimen and 94.8% for the thrice-weekly treatment, P=0.179). There were significant differences comparing the median number of sessions needed for clearance and the median cumulative doses, favouring the twice-weekly regimen (15 vs. 22, P=0.000, and 142.5 vs. 241.4 J/cm2, P=0.001, respectively). Conclusion: The treatment of psoriasis patients with twice- or thrice-weekly PUVA in this study was equally effective, the number of sessions required and the cumulative doses of UVA were lower with the twice-weekly regimen.