Anogenital warts are the most common sexually transmitted infection causing economic and psychosocial issues. Efficacy of zinc has been proved in treating nongenital warts, but its role in treating anogenital warts is not clear. This study was conducted to assess whether oral zinc gluconate in combination with cryotherapy effectively treated anogenital warts. A randomized double-blind, split-side, placebo-controlled trial was conducted on 50 patients suffering from genital warts. The patients were treated for 2 months with a combination of four sessions of cryotherapy and oral zinc gluconate versus placebos. Follow-up was performed at every 2 weeks based on the number of warts. The number of genital warts reduced significantly in both groups during treatment with cryotherapy, but no significant differences were observed between treatment with zinc and placebo. Patients in the zinc gluconate group reported significantly higher gastrointestinal adverse effects than those in the placebo group. This indicates that using oral zinc gluconate appeared to have no significant advantage over placebo in treating and reducing the number of genital warts; however, a longer duration of follow-up and pre-intervention serum level of zinc were necessary to evaluate the role of oral zinc therapy. (SKINmed. 2023;21:21-26).