Background: Transgender and gender-diverse people are at higher risk for drug use and drug use disorder than their cisgender peers. Theory and research have suggested that external minority stressors (e.g., discrimination, violence, and rejection) and internal minority stressors (e.g., internalized transphobia) may contribute to this health disparity. However, few studies have examined the proximal (e.g., same-day) association between minority stress and drug use. Methods: The present study tested the same-day association of external and internal minority stressors with use of drugs in a sample of 38 transgender and gender-diverse participants residing in two Southeastern cities. Participants reported their previous day's experiences with minority stress and drug use over the course of 30 days. A total of 836 daily surveys were collected (73.3 % compliance rate). Results: Multilevel modeling revealed that external minority stress (i.e., violence, harassment, discrimination, rejection), but not internalized stigma, was associated with increased odds of drug use on a given day, while controlling for time, same-day depressive affect and cognition, same-day gender dysphoria symptoms, demographics, and baseline levels of drug use. Conclusions: These findings suggest that external minority stress is associated with drug use on the same day. Future empirical and theoretical work may examine factors that could moderate these associations. Clinicians working with transgender and gender-diverse individuals should assess for minority stress and possible related drug use behavior.