Background The aim of this clinical trial was to assess the efficacy and safety of calcipotriol cream associated with oraletretinate compared with etretinate alone in the treatment of moderate-severe psoriasis.Methods This controlled multicenter trial, within patients (hemiparts), enrolled 86 in- or out-patients (62 males, 24 females),mean (LSD) age 57.1 5 14.2 years, with psoriasis vulgaris on both sides of the body, and mean (LSE) baseline PASI score(Psoriasis Area and Severity Index) 30.7 ? 0.9. All patients took oral etretinate 50 mg/day and applied calcipotriol cream (50kg/g) on one half of their body twice a day. Treatment was continued for 9 weeks, and patients were seen every 3 weeks.Results At the end of the first 3 weeks the PASI score indicated a significant clinical difference between the two sides of thebody (P < 0,001, ANOVA), with a reduction of 50.7% in the score for the calcipotriol-treated half, compared with a 39%reduction for the untreated half. By the 9th week of treatment the PASI score was 81.4% lower on the treated half, and 70.3% onthe untreated side (P < 0.001, ANOVA).Conclusions These findings suggest that patients with moderate-severe psoriasis might benefit from treatment with etretinateplus calcipotriol, with the aim of achieving a faster response and an overall smaller total dose of etretinate.