BACKGROUND Treatment of primary acquired cold urticaria (CU) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines. OBJECTIVE The objective of the study was to assess the efficacy and safety of mizolastine, an antihistaminic with antiallergic properties, versus placebo in primary acquired CU. METHODS This study was a phase II, multicenter, randomized, double-blind, crossover, placebo-controlled study of mizolastine (10 mg, once daily) versus placebo in 28 patients with primary acquired CU. Efficacy was measured by the cold-stimulation time test, the wheal response, and pruritus intensity after an ice-cube test. RESULTS Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity. Statistically significant differences were observed versus placebo for the cold-stimulation time test, wheal response at 3 and 10 minutes, and pruritus intensity (P =.006,.015,.009, and.005, respectively). No clinically relevant adverse events were reported. CONCLUSIONS Mizolastine (10 mg, once daily) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events. Results suggest that mizolastine may be effective in the treatment of CU.