Background and aim : Genital wart is a common sexually transmitted disease caused by different types of human papilloma virus (HPV). Cryotherapy is one of the most commonly used treatment options. Trichloroacetic acid (TCA) is another therapy commonly used in treatment of genital warts.Materials and methods: The objective of his study was to evaluate and compare the efficacy and adverse effects of TCA and cryotherapy (with liquid nitrogen). Sixty female patients with external genital warts were enrolled into this prospective clinical trial. Thirty of them received topical solution of 80% TCA and the other 30 received cryotherapy with liquid nitrogen, once a week, until complete clearance of lesions or a maximum duration of 8 weeks. Results: Twenty-seven patients (93.1%) of those who received up to eight treatments of cryotherapy had complete clearance of their warts, compared with 28 (96.5%) of patients who were treated with TCA (P>0.05). The mean duration for complete clearance was 4.4 weeks for TCA and 5.2 weeks for cryotherapy (P=0.5). Patients who received TCA experienced a significantly greater number of local inflammatory reactions (P=0.01). Conclusion: Both cryotherapy and TCA are effective treatments. In comparison, TCA showed its efficacy earlier during the course compared to cryotherapy. TCA is more likely to cause adverse reactions.