Transgender women are at high risk of acquiring HIV; however, limited data have previously been collected to quantify their risk across Sub-Saharan Africa. We identified potential risk factors of HIV infection among trans women, and characterized differences in HIV risks between trans women and gay men and other men who have sex with men (MSM) in eight Sub-Saharan African Nations (Burkina Faso, Côte d’Ivoire, The Gambia, Lesotho, Malawi, Senegal, Swaziland and Togo). Surveys gathered information on sexual orientation, gender identity, discrimination, mental health, sexual behavior and engagement in HIV-related treatment and care, and were accompanied by laboratory-confirmed HIV tests. HIV risk among trans women compared to cis-gender MSM was estimated using a mixed effect logistic regression model. Survey questions addressing stigma were summarized in three scales through factor analysis and included as covariates. We conclude that trans women experience greater amounts of stigma and a higher burden of HIV than cisgender MSM, indicating a need for dedicated epidemiologic assessment and differentiated implementation of HIV prevention, treatment and care programs.