OBJECTIVES: Persons who are homeless have significant health challenges and barriers accessing care. Secure messaging supports communication between patients and their providers through a web-based portal, but the acceptability of this technology among patients with high prevalence of substance use disorders (SUDs) is unknown. We examined secure messaging use among veterans with experiences of homelessness (VEHs), and determined factors associated with messaging use. METHODS: We conducted a cross-sectional analysis of responses to a national survey of VEHs, administered by mail from March to October 2018 (response rate = 40.2%). One item assessed secure messaging use and satisfaction. We used multivariable logistic regressions to model secure messaging use, controlling for sociodemographics, medical conditions, housing indicators, and mental health and SUD diagnoses. RESULTS: Of 5072 VEHs, 21% had ever used secure messaging and 87% of the subsample found messaging to be useful. Secure messaging was more commonly used by VEHs who were female, had some college education, those with ≥3 chronic medical conditions, depression, or posttraumatic stress disorder (all P < 0.001). Messaging was much less common for VEHs ages 55 to 64 or older, non-Latino Blacks, those receiving homeless-tailored primary care, and those with SUDs (all P < 0.001). VEHs with opioid use disorder were even less likely than those with other SUDs to use secure messaging (P = 0.047). CONCLUSIONS: Persons with homeless experiences might require assistance to engage with secure messaging technology. As health systems limit in-person care during a national pandemic, alternative solutions may be needed to facilitate health communications and prevent care disruptions for patients experiencing homelessness and SUDs.