Our purpose was to find out whether the addition of calcipotriol ointment (50 micrograms/g) to systemic treatment with acitretin produces additional therapeutic effects and thereby an acitretin-sparing effect, and further to investigate the safety and tolerability of this combination. A multicentre, randomized, double-blind placebo-controlled study was designed. Patients were randomized to receive calcipotriol or placebo. All patients were treated with a starting dose of 20 mg acitretin per day and doses were adjusted at 2-weekly intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The dose requirement for acitretin, clinical signs and adverse events were recorded. Seventy-six patients were randomized to treatment with calcipotriol 50 micrograms/g ointment twice daily and 59 patients to treatment with the vehicle only twice daily. Clearance or marked improvement was achieved by 67% of the patients in the calcipotriol group and by 41% of the patients in the placebo group (P = 0.006). Calcipotriol treatment proved to have a statistically significant additional effect to acitretin on the Psoriasis Area and Severity Index, redness, thickness and scaliness as compared with placebo. Clearance or marked improvement was achieved with a statistically significantly lower cumulative dose of acitretin by the patients in the calcipotriol group as compared with the placebo group. The number of patients reporting adverse events was pronounced and largely related to acitretin. No significant differences were observed between the two treatment groups with respect to adverse events. Laboratory assessments were essentially normal. The addition of calcipotriol ointment to acitretin treatment contributes to the efficacy, reduces the cumulative dose of acitretin to reach marked improvement or clearance, and is well-tolerated and safe.