BACKGROUND Cryotherapy and immunotherapeutic modalities elicit nonspecific immune response against the human papillomavirus. There is a paucity of literature on the effects of a sequential shift to immunotherapy in cryotherapy-resistant warts. OBJECTIVE To study the efficacy of intralesional purified protein derivative (PPD) immunotherapy in cryotherapy-resistant warts. METHODS Patients with cryotherapy-recalcitrant cutaneous warts were given intralesional injections of PPD into the index warts (oldest or largest) at 2-week intervals until complete clearance or up to a maximum of six injections. The response in the treated index and distant warts was defined as complete, partial, and no response (<25%). Complete responders were followed up for another 3 months to check for recurrence. RESULTS Twenty-eight patients completed the study protocol. Of the eight patients with single warts, four (50%), one (12.5%), and three (37.5%) patients had complete, partial, and no response, respectively. Of the 20 patients with multiple warts, nine (45%) had complete clearance of all warts, two (10%) each had complete and partial response in the index wart, respectively, with no response of the distant warts, and seven (35%) had no response in all warts. Complete response was seen in an average of 3.1 injections (range 1-5). There was no recurrence at the follow-up visit. CONCLUSIONS Immunotherapy with PPD has potential in producing regional and remote wart regression even in cryotherapy-resistant warts. It is a safe and economical modality in children, multiple warts, and difficult-to-treat warts.