Background: A variety of treatment modalities have been described for cutaneous warts. We sought to determine the safety and efficacy of a topical formulation of cantharidin, podophyllotoxin, and salicylic acid in the treatment of plantar warts. This combination treatment is widely used in Europe and elsewhere but has not been described in the podiatric medical literature. Methods: A retrospective study was conducted of 144 patients with simple or mosaic plantar warts who were treated with a topical, pharmacy-compounded solution of cantharidin, 1%; podophyllotoxin, 5%; and salicylic acid, 30%. All of the patients, aged 8 to 52 years (mean ± SD, 20.9 ± 11.0 years), were treated according to the authors3 standard protocol. Of the 144 patients, 92 were being treated for the first time. None of the 52 previously treated patients had received more than one other type of treatment in the past. Results: After 6 months of follow-up, complete eradication of the plantar warts was noted in 138 of the 144 patients (95.8%). Of these patients, 125 (86.8%) required a single application of the solution, and 13 (9.0%) needed two or more applications. No significant adverse effects or complications were observed. Conclusion: A topical solution of cantharidin, podophyllotoxin, and salicylic acid was found to be safe and effective in the treatment of simple and mosaic plantar warts. This formulation is a promising alternative treatment modality for plantar warts. (J Am Podiatr Med Assoc 98(6): 445–450, 2008)