The aim of this double-blinded, vehicle-controlled study was to test the antipruritic efficacy of topical strontium to relieve a nonhistaminergic form of itch that would be clinically relevant for chronic pruritic diseases. Itch induced with cowhage is mediated by PAR2 receptors which are considered to play a major role in itch of atopic dermatitis and possibly other acute and chronic pruritic conditions. The topical strontium hydrogel formulation (TriCalm®) was tested in a head-to-head comparison with 2 common topical formulations marketed as antipruritics: hydrocortisone and diphenhydramine, for their ability to relieve cowhage-induced itch. Topically-applied strontium salts were previously found to be effective for reducing histamine-induced and IgE-mediated itch in humans. However, histamine is not considered the critical mediator in the majority of skin diseases presenting with chronic pruritus. The current study enrolled 32 healthy subjects in which itch was induced with cowhage before and after skin treatment with a gel containing 4% SrCl2, control vehicle, topical 1% hydrocortisone and topical 2% diphenhydramine. Strontium significantly reduced the peak intensity and duration of cowhage-induced itch when compared to the control itch curve, and was significantly superior to the other two over-the-counter antipruritic agents and its own vehicle in antipruritic effect. We hereby show that a 4% topical strontium formulation has a robust antipruritic effect, not only against histamine-mediated itch, but also for non-histaminergic pruritus induced via the PAR2 pathway, using cowhage.