Purpose: Studies on drug use in transgender populations, particularly those in resource-limited settings, are scarce. Considering that drug use can be a coping mechanism to deal with stigma and traumatic experiences, we examined associations between stigma, trauma, and drug use in a national sample of transgender women from the Dominican Republic. Methods: Bivariate analyses examined differences between drug users and abstainers (n=287). Multivariate analyses reported odds ratios (OR) with general drug, marijuana, and cocaine use as outcomes (n=243). Results: A quarter of respondents (24.5%) experienced sexual abuse, 12.1% were tortured, and 20.1% experienced a murder attempt. More than a quarter reported using illegal drugs (26.1%). Drug users had lower socioeconomic status; 30.0% of drug users had a primary level of education or less (18.2% of abstainers) and 17.6% of drug users had higher income, defined as greater than 10,001 pesos (∼$210 United States Dollars, USD) per month (28.1% of abstainers). More than half of drug users experienced some form of trauma (51.4%) compared to 43.5% of abstainers, and 28.4% of drug users, compared to 17.1% of abstainers, experienced a murder attempt on her life. Independent sample t-tests found significant differences between drug users and abstainers. Transgender women who experienced sexual abuse had three times high odds of using cocaine. Drug users were more likely to have experienced sexual abuse and attempted suicide (p<0.05 for both). Respondents who attempted suicide had higher odds of using drugs generally and using marijuana specifically, compared to respondents who had not attempted suicide (OR=2.665 and 3.168, respectively). Higher scores on the stigma scale were associated with higher odds of any drug use and cocaine use (OR=1.132 and 1.325, respectively). Conclusions: Although some nations have implemented antidiscrimination policies protecting transgender citizens, these policies are not consistently enforced. Eliminating stigma and stigmatizing policies may reduce rates of drug use as a coping mechanism.