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This study provides a systematic review of existing research that has empirically evaluated interventions designed to reduce stigma related to substance use disorders.A comprehensive review of electronic databases was conducted to identify evaluations of substance use disorder related stigma interventions. Studies that met inclusion criteria were synthesized and assessed using systematic review methods.Thirteen studies met the inclusion criteria. The methodological quality of the studies was moderately strong. Interventions of three studies (23%) focused on people with substance use disorders (self-stigma), three studies (23%) targeted the general public (social stigma) and seven studies (54%) focused on medical students and other professional groups (structural stigma). Nine interventions (69%) used approaches that included education and/or direct contact with people who have substance use disorders. All but one study indicated their interventions produced positive effects on at least one stigma outcome measure. None of the interventions have been evaluated across different settings or populations.A range of interventions demonstrate promise for achieving meaningful improvements in stigma related to substance use disorders. The limited evidence indicates that self-stigma can be reduced through therapeutic interventions such as group-based acceptance and commitment therapy. Effective strategies for addressing social stigma include motivational interviewing and communicating positive stories of people with substance use disorders. For changing stigma at a structural level, contact-based training and education programs targeting medical students and professionals (e.g. police, counsellors) are effective.