Cigarette smoking may decrease serum levels of vitamin D and reduce its efficacy. We aimed to evaluate the safety and efficacy of intralesional vitamin D in the treatment of warts and to investigate the effect of smoking on its efficacy in these cases. The study included 20 patients with verruca vulgaris and deep palmoplantar warts. The wart to be injected was cleaned by alcohol and then injected with 0.1 mL of prilocaine (20 mg/mL). 0.2 mL of vitamin D3 (7.5 mg/mL) solution was slowly injected into the base of each wart. The maximum total amount of vitamin D3 injected into a patient in one session was 7.5 mg. The injection was done at 4 weeks interval until clearance or for a maximum of two sessions. Clinical and dermoscopic follow‐up of the treated and distant warts was carried out. Forty percent of the treated lesions showed complete clearance and the rate of distant wart response was 17.65%. Among different demographic and clinical variables in the studied patients, smoking and older age seemed to decrease the therapeutic response Intralesional vitamin D is effective in the treatment of warts, however, smoking and aging may reduce its efficacy.