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The use of substances inhibits individuals’ decision-making capabilities, and in some instances, may lead to more serious offending. Although prior research identifies substance use as an important predictor of crime, there is limited research examining how the use of multiple substances influences the severity of the crime. This study examines whether there is an association between polydrug use, such as using cocaine and methamphetamines at one time, on offense severity, grouped by crimes against persons, crimes against property or crimes against society. Using data from the Survey of Prison Inmates (2016) we examine whether there are differences in offense severity between polysubstance users and then we examine whether there are differences among the individuals who reported being under the influence of the same combinations of substances at the time of the offense. We conclude with implications for policy and future research.