An association between psoriasis and cardiovascular diseases has been reported, and treatment of this condition is often considered difficult because the conventional systemic therapies often show several side effects. To assess the efficacy and tolerability of a new drug, folinate calcium, to treat psoriasis, a total of 58 patients affected by active psoriasis were enrolled in a variable period study. These patients had clinically stable, plaque psoriasis involving greater than or equal 6% body surface area. Thirty of these patients were treated with folinate calcium therapy, 15 mg orally once daily, for a variable period based on each patients clinical response. The comparison was made with 28 psoriatic patients treated with conventional systemic therapies (cyclosporine, acitretin, etanercept, efalizumab, infliximab, adalimumab). A clinical improvement was observed in both group, but in the first one we did not observe any side effects, whereas some important side effects were observed in the second. These preliminary results support the effectiveness and tolerability of folinate calcium treatment in psoriasis.