The purpose of this study is to improve understanding of HIV vulnerability and opportunities for HIV prevention within the social networks of male-to-female transgender persons in San Salvador, El Salvador. We compare HIV prevalence and behavioral data from a sample of gay-identified men who have sex with men (MSM) (n = 279), heterosexual or bisexual identified MSM (n = 229) and transgender persons (n = 67) recruited using Respondent Driven Sampling. Transgender persons consistently reported higher rates of HIV risk behavior than the rest of the study population and were significantly more likely to be involved in sex work. While transgender persons reported the highest rates of exposure to HIV educational activities they had the lowest levels of HIV-related knowledge. Transgender respondents' social networks were homophilous and efficient at recruiting other transgender persons. Findings suggest that transgender social networks could provide an effective and culturally relevant opportunity for HIV prevention efforts in this vulnerable population.