: Substance use (SU) is associated with physical injury and mental health disorders in older persons, but recent research has scarcely examined SU in U.S. Vietnam-era veterans who are mostly in or near their eighth decade of life. : We compared the prevalence of self-reported lifetime and current SU and modeled current usage patterns in a nationally representative sample of veterans versus a matched nonveteran cohort. : Cross-sectional, self-reported survey data were analyzed from the 2016-2017 Vietnam Era Health Retrospective Observational Study (VE-HEROeS) ( = 18,866 veterans,  = 4,530 nonveterans). We assessed lifetime and current alcohol and drug use disorders; lifetime and current use of cannabis, opioids, stimulants, sedatives, "other drugs" (psychedelics, prescription or over-the-counter drugs not prescribed/used as intended); and current SU patterns (alcohol-use-only, drug-use-only, dual-SU, no SU). Weighted descriptive, bivariable, and multivariable statistics were calculated. Covariates in multinomial modeling included sociodemographic characteristics, lifetime cigarette smoking, depression, potentially traumatic events (PTEs), and current pain (SF-8). : Prevalence of lifetime opioid and sedative use ( ≤ .01), drug and alcohol use disorders ( < .001), and current "other drug" use ( < .001) were higher in veterans versus nonveterans. Current use of alcohol and cannabis was high in both cohorts. In veterans, very severe/severe pain, depression, and PTEs were highly associated with drug-use-only ( < .001) and dual-SU ( < .01), but these associations were fewer for nonveterans. : This research confirmed existing concerns over substance misuse in older individuals. Vietnam-era veterans may be at particular risk due to service-related experiences and later-life tribulations. Era veterans' unique perceptions toward healthcare assistance for SU may need greater provider focus to maximize self-efficacy and treatment.