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OBJECTIVE: Some US military service members who have never been deployed experience negative emotions related to never having been deployed, and some work shows these non-deployment emotions (NDE) are cross-sectionally associated with hazardous drinking for male, but not female, US Army Reserve/National Guard (USAR/NG) soldiers. However, it is not known if these effects extend to drug use or persist longitudinally, which is the focus of the current study. DESIGN: A longitudinal residual change analysis of a subset of data (N = 182 never-deployed soldiers) from Operation: SAFETY, an ongoing survey-based study of USAR/NG soldiers recruited from units across New York State. MAIN OUTCOME MEASURES: Current tobacco use, non-medical use of prescription drugs [NMUPD], current cannabis use, and other current illicit drug use (excluding cannabis) at four time points over a 3-year period RESULTS: Results from bootstrapped residual change generalized estimating equation (GEE) models show that more negative NDE were longitudinally associated with a greater likelihood of current NMUPD among male, but not female, soldiers (p < 0.05). NDE were not longitudinally associated with current tobacco use, cannabis use, or other illicit drug use among male or female soldiers (ps > 0.05). CONCLUSION: NDE may contribute to ongoing NMUPD among male USAR/NG soldiers who have never been deployed. Never-deployed soldiers, especially those with negative emotions related to never having been deployed, should not be overlooked in military screening and intervention efforts.