Abstract Cutaneous warts, caused by human papillomavirus, are common benign skin lesions with various treatment options, including immunotherapy, which has gained attention for its ability to stimulate cell-mediated immunity and promote wart clearance. This study compared the efficacy and safety of intralesional injections of Vitamin D3, MMR vaccine, and acyclovir in the management of verruca vulgaris. A total of 105 patients were divided into three groups, each receiving intralesional injections of one of the treatments at two-week intervals, with a maximum of three sessions. The results showed that while initial improvements after the first session were comparable across all groups, significant differences emerged after the final session. The MMR group demonstrated superior efficacy, with 57.14% of patients achieving excellent improvement, com- pared to 28.57% in the Vitamin D3 group and 42.85% in the acyclovir group (p=0.00105). Additionally, the MMR group had the lowest proportion of patients with no improvement (11.42%), compared to the Vitamin D3 group (20%) and the acyclovir group (57.1%) (p=0.0045). Safety profiles also favored the MMR vaccine, which showed fewer adverse effects compared to Vitamin D3 and acyclovir. The findings suggest that intralesional MMR is a more effective and safer treatment option for cutaneous warts than intralesional Vitamin D3 or acyclovir. This supports the growing evidence for immunotherapy as a promising approach in managing cutaneous warts.