Abstract: U.S. Army National Guard and Army Reserve (ANG/USAR) soldiers are at risk for substance use, and research in other populations suggests risk-related behaviors and traits affect the propensity for use. Less is known about how deployment might amplify these effects. Our research explored the relations between risk-related behaviors and substance use among ANG/USAR soldiers and investigated differences by deployment (previously vs. never deployed). We drew a subset of data from Operation: SAFETY, an ongoing study of ANG/USAR soldiers and their partners (married/living together as if married). Cross-sectional regression models examined domains of risk (i.e., risk perception, risk-taking/impulsivity, sensation-seeking) and substance use (any current drug use, current non-medical use of prescription drugs, current illicit drug use, alcohol problems, and frequent heavy drinking [FHD]). Final models controlled for age, sex, anger, and PTSD. Interaction terms between risk behaviors and deployment status on substance use were also noted. Results revealed that greater risk perception was significantly associated with a lower likelihood of and protective against FHD. Greater risk-taking/impulsivity was associated with a higher likelihood of any current drug use and alcohol problems. Additionally, interaction models suggest that non-deployed soldiers at every level of risk-taking/impulsivity had a consistently high likelihood of illicit drug use overall. Sensation-seeking was not associated with any outcome. Findings demonstrate that greater risk-taking/impulsivity was associated with substance use, and never deployed/non-deployed ANG/USAR soldiers might be more vulnerable. Our work can help inform substance use interventions in the military by highlighting the role and impact of risk-related behaviors and non-deployment.