Human papillomavirus (HPV) is one of the most common sexually transmitted diseases (STDs) and is frequently presented clinically as anogenital warts in both males and females. There is a high rate of transmission of HPV in female partners of men with pre-existing penile warts, and HPV infection in men has been shown to contribute to HPV infection and subsequent cervical disease in women. HPV is associated with significant morbidity and represents a substantial healthcare burden. Data indicate that males experienced a longer duration of genital warts and incurred greater treatment costs than women. The quadrivalent vaccine, the first vaccine to be approved for use in adolescent and young women aged 9 to 26 years for the prevention of cervical cancer and genital warts, targets HPV types -6, and -11 (responsible for genital warts), and HPV types-16 and -18 (involved in cervical cancer). Pharmacoeconomic data determined that routine administration of a prophylactic quadrivalent HPV vaccine to 12-year-old males and females in addition to catch-up vaccination of 12- to 24-year-old males and females, within the setting of organized cervical cancer screening within the US, was the most cost-effective strategy. It is also anticipated that widespread use of vaccines that offer protection against HPV-6 and -11 could potentially reduce the workload at STD clinics by approximately 10% without a substantial impact on the diagnosis and treatment of other STDs. To optimally control transmission of HPV, consideration should be given to vaccinating males as well as females.