Background: Warts are a common skin condition that affects people all over the world. This ailment affects 2–20% of students in primary school. A well-known keratolytic agent, potassium hydroxide (KOH), has many dermatological uses. Vitamin D is important in the proliferation and differentiation of keratinocytes. Objective: The aim of the current work was to compare the efficacy and safety of intralesional vitamin D3 injections and 5% KOH cream separately and in combination with each other in the treatment of warts. Patients and Methods: This study was carried out at the private outpatient Al- Ahlam Center of Dermatology and Cosmetology in Gharyan, Libya from 1^st of Sep to last of Dec 2021. 45 patients with warts were included in the study. They were classified into 3 groups according to method of treatment into Vitamin D3 group, 5% KOH cream group, and combination group. Results: The mean age of patients was 27.04 ± 11.7 years. 31 patients completed the study. Complete response was seen in 12 patients with vitamin D injection after period of 4 months, 9 patients with 5% KOH cream after period 2-3 months, and 10 patients with combination both treatment after a period of 1 month. Conclusions: It could be concluded that intralesional vitamin D with 5% KOH cream is safe, effective, and inexpensive treatment option for recalcitrant palmoplantar and periungual warts.