Purpose Human papillomavirus (HPV) is the most common sexually transmitted infection globally and is responsible for a variety of cancers in men and women. An effective HPV vaccine licensed for use in girls and boys has been indicated forbut is not widely implemented in men who have sex with men (MSM). Limited data are available for transgender women (TW). We explored the social and behavioral aspects related to HPV vaccine uptake and participation in HPV vaccine studies among Peruvian MSM and TW. Methods Focus groups and individual in-depth interviews were conducted to obtain the knowledge, thoughts, and opinions from Peruvian MSM and TW regarding HPV vaccination. Data were analyzed using systematic comparative and descriptive content analysis. Results Three focus groups and fifteen individual in-depth interviews were conducted among 36 MSM and TW. Participant mean age was 26 years (range 18±40). Though many participants were unfamiliar with HPV vaccination, most expressed positive attitudes. Participants expressed concerns about the potential for stigma when disclosing HPV vaccination. Conclusion Peruvian MSM and TW felt that HPV vaccination would be acceptable to themselves and their peers. Nonetheless, vaccine intake may be impeded by potential stigma. Findings from this study may guide HPV vaccine implementation in similar populations.