Objectives To evaluate the results of randomised controlled trials (RCTs) regarding the efficacy of human papillomavirus (HPV) vaccination in preventing male genital‐related diseases. Methods A systematic search of English language literature using PubMed, Scopus, and Cochrane Library was performed in April 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) protocol. Results Evidence from four RCTs (including 7008 male participants) support the efficacy of the quadrivalent HPV vaccine in preventing genital warts and persistent HPV infection in HPV‐naïve men. The low incidence of male genital malignancies in the control groups of the reported studies lead to underpowered evidence. However, vaccination leads to durable protection with a long‐term follow‐up of 10 years showing efficacy of 91.8% to prevent HPV 6‐, 11‐, 16‐, or 18‐related external genital lesions (EGLs) in HPV‐naïve subjects. Additionally, the quadrivalent vaccine seems to effectively reduce the detection of DNA from all four HPV types. Conclusion In summary, early quadrivalent HPV vaccination demonstrates efficacy in preventing HPV infection and EGLs in males. Well controlled prospective studies are needed to confirm the long‐term efficacy, specifically in cancer prevention, in all men and specific subject subgroups, and to identify the targeted population who is most likely to benefit from early vaccination.