Background: Multiple viral warts represent a frustrating challenge for both patients and physicians. Management is difficult, primarily due to recalcitrance to standard therapy and high recurrence rates. Recently, intralesional antigen immunotherapy has shown promising efficacy in the treatment of warts. Objective: The aim of our study was to compare efficacy and safety of intralesional PPD versus measles, mumps, and rubella (MMR) vaccine in the management of multiple warts. Materials and methods: One hundred and five patients having multiple warts were randomly divided into group A (PPD), group B (MMR) and group C (normal saline), with 35 patients in each group. In each group, the largest wart was injected intralesionally with 0.1 mL of vaccine at 2 weeks interval until complete clearance or for a maximum of 8 weeks. Results: Out of 105 patients enrolled in the study, 27, 25, and 21 patients completed the study in group A, group B, and group C, respectively. Rest were lost to follow up due to various reasons such as pain and long treatment duration. Complete clearance was seen in 14 patients (51.85%) in group A, 14 patients (56%) in group B, and 0 patients in group C. Partial clearance was seen in four patients (14.81%) in group A, four patients (16%) in group B, and three (14.28%) patients in group C. Nine patients (33.33%) in group A, seven patients (28%) in group B and 18 (85.71%) patients in group C did not respond to immunotherapy. Conclusions: Intralesional immunotherapy by both vaccines is a promising, effective, and safe treatment modality with MMR having slight edge.