Intimate partner violence (IPV) is a pervasive public health problem in which transgender individuals are at elevated risk. The present study examined associations among IPV, demographics, sex work, and substance use in a national sample of transgender individuals. National data from the 2015 Transgender Survey ( n  = 27,715) was analyzed. Results indicated that nearly half (48.3%) of transgender individuals had experienced IPV in their lifetime. Lifetime IPV differed significantly based on demographics, sex work and substance use. Individuals at highest risk for lifetime IPV were those who self-identified as a trans man, were 25–64 years old, were Native American/Alaskan Native or Middle-Eastern/North African, had some college or less, had an annual income of $1–$24,999, had been part of a religious/spiritual community, had engaged in sex work and had used substances. Public and community health efforts are needed to address risk factors contributing to transgender involvement in IPV. Primary and secondary preventive measures are needed to effectively combat IPV. Primary prevention strategies should educate individuals regarding IPV, healthy relationships and the adoption of healthy coping and communication skills. Secondary prevention strategies should utilize screening procedures to identify individuals at risk and bolster social connectedness. Treatment programs should be developed to reduce IPV among individuals who use substances. Future research is strongly needed in this area.