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/cm 2 , 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.