BACKGROUND Plantar warts are refractory to any form of treatment. High cure rates have been reported with a topical proprietary formulation consisting of 1% cantharidin, 5% podophyllotoxin and 30% salicylic acid (CPS). However, no data exists comparing the efficacy of this formulation with another treatment. Cryotherapy is a method that is also widely used in the treatment of plantar warts. Likewise, there is no evidence that it is more effective than any topical treatment. OBJECTIVE We aim to compare the efficacy of topical CPS and cryotherapy in the treatment of plantar warts. METHODS Patients with plantar warts were consecutively treated with either cryotherapy or topical CPS. Both treatments were performed every 2 weeks for up to five sessions. In patients without complete clearance, the therapy was switched to the other treatment option. RESULTS Twenty-six patients with a total of 134 warts were included. Fourteen patients were completely cleared of their warts with topical CPS, whereas only in five of 12 patients (41.7%) warts were completely cleared with cryotherapy (P=0.001). In seven patients without complete clearance, the therapy was switched to CPS. Four of these patients missed the follow-up. While the two of the remaining three patients were cleared of their warts, one patient's warts still failed to clear. CONCLUSIONS Topical CPS is more effective than cryotherapy in the treatment of plantar warts.