© 2017 Budhwani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: Not only do transgender female sex workers have some of the highest rates of sexually transmitted infections (STI), human immunodeficiency virus (HIV), and experienced stigma, they also have higher likelihood of early sexual debut and some of the lowest levels of educational attainment compared to other stigmatized populations. Some of the most common interventions designed to reduce transmission of HIV and STIs seek to educate high-risk groups on sexual health and encourage condom use across all partner types; however, reaching stigmatized populations, particularly those in resource-limited settings, is particularly challenging. Considering the importance of condom use in stopping the spread of HIV, the aim of this study was two-fold; first to characterize this hard-to-reach population of transgender female sex workers in the Dominican Republic, and second, to assess associations between their HIV knowledge, experienced stigma, and condom use across three partner types. Methods: We analyzed self-reported data from the Questionnaire for Transgender Sex Workers (N = 78). Respondents were interviewed at their workplaces. Univariate and bivariate analyses were employed. Fisher Chi-square tests assessed differences in HIV knowledge and experienced stigma by condom use across partner types. Results: HIV knowledge was alarmingly low, condom use varied across partner type, and the respondents in our sample had high levels of experienced stigma. Average age of first sexual experience was 13.12 years with a youngest age reported of 7. Dominican Republic statutory rape laws indicate 18 years is the age of consent; thus, many of these transgender women’s first sexual encounters would be considered forcible (rape) and constitute a prosecutable crime. On average, respondents reported 8.45 sexual partners in the prior month, with a maximum of 49 partners. Approximately two thirds of respondents used a condom the last time they had sex with a regular partner. This was considerably lower than condom use reported with coercive partners (92.96%) and clients (91.78%). Bivariate analyses revealed two trends: experienced stigma was associated with lower rates of condom use, and lower HIV knowledge was associated with lower rates of condom use. The former provides additional evidence that experienced stigma may become internalized, affecting individual-level behaviors—lowering self-confidence and resilience—making it more difficult to negotiate condom use due to lack of self-efficacy and desire to show trust in one’s partner. The latter supports public health research that suggests gaps in HIV knowledge persist and are pronounced in highly stigmatized populations. Discussion: The vulnerabilities experienced by transgender persons, particularly in environments that vehemently adhere to conservative ideologies related to sex and gender, are significant and harm this population. These vulnerabilities could potentially be addressed through critically examining of impact of policies that indirectly promote or allow victimization of transgender citizens and subsequently diminish the effectiveness of public health and educational interventions. By taking action through the revocation of such laws, the Dominican Republic has the opportunity to improve overall population health, to protect some of its most stigmatized citizens, and to become the flag bearer of enhanced human rights in the Caribbean and Latin America.