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Introduction: Substance use can be the source of various disabilities. The purpose of this study is to investigate and compare the disabilities caused by substance use. Material and methods: This is a descriptive-analytical cross-sectional study. The samples studied in this study were 400 people who referred to MMT centers in Hamadan, Iran. Centers were selected by cluster sampling method and samples within the cluster were selected by convenience sampling method. The instrument was the WHODAS2 standard questionnaire designed by the World Health Organization to assess disability. The extracted data were analyzed by SPSS20 software. Result: 64.8% of the participants were opium users, 24.5% amphetamine users and 10.8% were marijuana users. The results showed that age, gender, place of residence and type of substance use were significantly associated with the degree of disability and the highest rate of disability occurred in opium users (p ≤ .01). Conclusion: Different substances differ in the amount and type of disabilities they cause and this difference should be considered in the treatment of people with substance use disorder. [ABSTRACT FROM AUTHOR]