The aim of our study was to evaluate the efficacy and safety of topical cantharidin–podophylotoxin–salicylic acid (CPS) treatment of recalcitrant plantar warts (RPW). This study was carried out in a health center in the city of A Coruña (Spain) between January and December 2013. A total of 75 patients completed all the stages of the research process. Information related to treatment with CPS and adverse effects was abstracted from medical records. Of 93 potential patients identified, 75 had at least one follow-up visit or telephone call after treatment and were included in this study. Patients experienced an average of 5.4 visits until complete resolution of their plantar wart occurred, although CPS was not applied at every visit. Fifty-four patients required one application to eliminate the wart and 21 patients required two applications/patient. Seventy-seven percent of patients experienced blistering – an expected therapeutic side effect. All patients experienced some form of an adverse event, the most common being pain (81.3%) and significant blistering (15%). Other side effects were rare (18.7%) and included pruritus, possible mild infection, significant irritation, and bleeding. All patients reported treatment, supporting our results that CPS is a safe and efficacious treatment modality for RPW and should be considered when symptomatic infection necessitates treatment.