Introduction: Minority stress theories suggest that high rates of discrimination experienced by transgender people are precipitants of substance use. This risk is likely exacerbated by an inadequate provision of trans-inclusive substance misuse services. However, the exclusion of transgender people from the general substance misuse literature makes it difficult to determine the extent to which transgender status influences substance use. A systematic review was undertaken to better understand the prevalence, patterns and correlates of substance use among this group. Methods: In accordance with the PRISMA guidance, a literature search was conducted to 29th May 2019 on PubMed, PsycINFO, Embase and Global Health databases. Primary quantitative studies, published in English, that reported the prevalence, patterns or correlates of substance use by transgender people were included, with no restriction on methodological design. Results: 653 unique records were identified, and 41 studies were included. Half the studies reported on both transgender men and transgender women and half transgender women only. There was high and excess prevalence of substance use among transgender compared with cisgender people, but insufficient evidence to estimate prevalence or quantify the risk for substance use. Correlates of substance use included transphobic discrimination or violence, unemployment and sex work, gender dysphoria, high visual gender non-conformity and intersectional sexual minority status. Conclusions: The sparse findings lend support to the minority stress model. However, the overreliance of the literature on disproportionate investigation of transgender women with multiple intersectional disadvantages, means there are significant gaps regarding the wider transgender community. To ensure substance use treatment services are inclusive, gender identity should be recorded and targeted interventions available. Clinicians should be aware of the multiple, complex drivers of substance use and be prepared to ask about substance use and offer support. Given the high prevalence of trauma experienced by transgender people, trauma-informed psychosocial interventions may be useful in the management of problematic substance use in transgender adults.