The aim of this study was to compare the efficacy of crotherapy versus imiquimod 5% in the treatment of anogenital warts. Eighty HIV-negative males were included in the analysis; 35 of them were treated with imiquimod 5% three times a week for 6-10 hours and 45 of them with cryotherapy once in three weeks. Follow-up appointments were arranged every month for the first three months and then at six and 12 months, or in between whenever the patients noticed any signs of recurrence. Treatment for both groups was continued for a total of 12 weeks or until the warts cleared. At the end of three months, irrespective of the type of treatment, 78.8% of the patients demonstrated 100% improvement. Cryotherapy was more effective, as 86.7% of patients showed 100% improvement compared with 68.6% of patients in the imiquimod group. On the contrary, 17.1% of the imiquimod group did not show any signs of improvement, compared with 2.2% of the cryotherapy group (P = 0.017). However, patients treated with imiquimod tended to improve earlier than patients on cryotherapy (P = 0.012). No statistically significant difference was observed regarding the recurrence rate between the two groups (P = 0.138). Treatment with imiquimod was less painful than cryotherapy (P = 0.034). Cryotherapy was more effective than imiquimod 5% for the treatment of anogenital warts in males but was more inconvenient.