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Substance dependence is a long-standing issue of criminological significance, yet life-course criminology only rarely engages with the issue. Criminologists have identified a myriad of ways substance use impacts changes in offending. However, the influence of more problematic and persistent forms of substance use, such as dependence which may hinder key developmental life transitions and increase the frequency of traumatic victimization events, remains underexplored. The objective of this study is to examine the direct and indirect impact of substance dependence, life transitions (e.g. attainment of stable employment, involvement in quality romantic relationships, and embeddedness in prosocial peer networks), and victimization on within-person changes in offending. Using data from the Pathways to Desistance study, I use fixed-effects regression to examine this objective. I find that substance dependence significantly explains changes in offending and that the substance dependence-offending relationship is partially explained by life transitions and victimization events. These results elaborate on mechanisms that link substance use to prolonged criminal careers and advance understanding about the interplay between substance use, life transitions, and criminal behavior during the transition to adulthood.