Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and more than 100 types of HPV have been identified. This systematic review was carried out to assess whether vaccinating boys with the same HPV vaccines currently offered to 11- to 12-year-old girls in Norway would be effective in preventing HPV-related diseases among males. The five included references represent two different clinical trials. The efficacy data is from one large randomized study that examined the efficacy of prophylactic vaccination of males aged 16 to 26 with the quadrivalent HPV vaccine. This study shows that the quadrivalent vaccine is efficacious in preventing external genital lesions, caused by infection with HPV 6, 11, 16 or 18, in males aged 16-26 (moderate quality of evidence). Genital warts are the main type of genital lesions prevented by vaccinating males (moderate quality evidence). Effect data on precancerous lesions such as penile intraepithelial neoplasia (PIN2+) are sparse because of limited (three years) follow-up, and the results are not conclusive (low quality evidence). Assessement of precancerous lesions probably needs longer follow-up time. In the subpopulation of men who have sex with men, the vaccine reduced the risk of anal intraepithelial neoplasia (AIN2+) (low quality evidence). Three years follow-up after HPV vaccination indicated little or no difference in the occurrence of serious adverse events in the vaccine group compared to the control group (moderate quality of evidence). Long-term follow-up studies are required to demonstrate if there is an effect of HPV vaccination on cancer related mortality and cancer prevalence ( penile, anal or oropharyngeal cancer).