Abstract Background External genital warts (EGWs) are benign epidermal growths on the anogenital regions, which can occur in both women and men. They are caused by the human papillomavirus (HPV). More than 90% of cases of anogenital warts are caused by HPV types 6 and 11.There are several different ways to treat genital warts with varying degrees of success. However, till now no definitive treatment has emerged as the ideal standard of care in the treatment of genital warts and this has developed the need for new ways and modalities to help manage genital warts more efficiently. Objective To evaluate and verify efficacy, safety and tolerability of intralesional ionic anti-viral injection of combined furosemide and digoxin in treatment of multiple resistant genital warts. Patients and Methods This study included 30 patients divided into 2 groups, 15 patients each, the study group received intralesional injection of combined digoxin and furosemide, one injection every week for maximum 5 injection sessions (5 weeks). 0.3 ml of combined digoxin and furosemide solution was slowly injected into the base of each wart with maximum 5 warts in the session, and the other group received intralesional saline as a control group. Results Both groups demonstrated insignificant differences regarding all demographic characteristics (age, sex, size of warts before treatment, number of warts before treatment and number of sessions) as well as duration of disease. The treatment used in this study was safe and tolerable with no systemic exposure with regards to the cardiac system (by ECG before and after treatment). Future studies are recommended on larger number of the patients with multiple genital warts. It might be helpful to try increasing the number of treatment sessions, increasing the number of warts treated per session, decreasing the interval between the sessions or increasing the concentration of the active treatment. Conclusion Intralesional injection of combined digoxin and furosemide wasn’t effective intreatment of genital warts.