Background: Current treatment strategies of psoriasis are not completely satisfactorily. By inhibiting inflammatory cytokines, nicotinamide may enhance the effects of current topical treatments. We investigated whether the combination of topical calcipotriol and nicotinamide is more effective than calcipotriol alone in treatment of psoriasis.Methods: Adult patients with mild to moderate psoriasis were randomized to receive topical calcipotriol 0.005% and nicotinamide 4% in combination or calcipotriol 0.005% alone, twice daily for 12 weeks. Patients were visited by a dermatologist at baseline and then, after the first and third months of therapy; and psoriasis severity was evaluated using the modified psoriasis area and severity index (PASI). Also, patient’s satisfaction was evaluated at the end of the trial using a 10-point rating scale.Findings: Sixty five patients (35 men) with the mean age of 36.5 ± 8.5 years completed the trial. Lesions on both sides were similar regarding baseline PASI score. At the end of the trial, PASI score was more reduced with calcipotriol + nicotinamide (83.6 ± 7.9 percent) compared to calcipotriol alone (77.8 ± 9.7 percent) (P < 0.001). Patients were also more satisfied with the improvement of lesions with calcipotriol + nicotinamide compared to calcipotriol alone (P < 0.001). Side effects included mild erythema and pruritus (4.6%) and moderate burning and sensitivity to light (3.0%).Conclusion: Nicotinamide can enhance the efficacy of calcipotriol when used in combination for topical psoriasis treatment, and it may be a good adjuvant to the current treatment regimens of psoriasis.