Objective: A comparison of efficacy, safety and tolerance of a twice-daily application of calcitriol 3 μg/g ointment with dithranol cream. Methods: The study was an 8-week, prospective, randomised, open, parallel-group trial with 114 patients. Subjects received either 3 μg/g calcitriol ointment (twice daily) or 0.25–2% dithranol cream (once daily for 30 min). Results were measured using global improvement, global severity, PASI, quality of life (QOL) and Psoriasis Disability Index scores. Safety was determined from reports of adverse events and blood chemistry analysis. Results: At final assessment, calcitriol and dithranol were comparably efficacious. Skin irritation was reported by 5% of calcitriol and 72% of dithranol patients. Patients rated QOL and overall acceptability of calcitriol more highly. Conclusions: Twice-daily calcitriol ointment (3 μg/g) is equally effective as a once-daily, short-contact dithranol regimen. However, calcitriol is better tolerated than dithranol, and provides a better QOL and a greater patient acceptability.