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Aim Individuals with anorexia nervosa (AN) often present with substance use and substance use disorders (SUDs). However, the prevalence of substance use and SUDs in AN has not been studied in-depth, especially the differences in the prevalence of SUDs between AN types [e.g., AN-R (restrictive type) and AN-BP (binge-eating/purge type]. Therefore, this systematic review and meta-analysis aimed to assess the prevalence of SUDs and substance use in AN samples. Method Systematic database searches of the peer-reviewed literature were conducted in the following online databases: MEDLINE, PsycINFO, Embase, and CINAHL from inception to January 2021. We restricted review eligibility to peer-reviewed research studies reporting the prevalence for either SUDs or substance use in individuals with AN. Random-effects meta-analyses using Freeman–Tukey double arcsine transformations were performed on eligible studies to estimate pooled proportions and 95% confidence intervals (CIs). Results Fifty-two studies met the inclusion criteria, including 14,695 individuals identified as having AN (mean age: 22.82 years). Random pooled estimates showed that substance use disorders had a 16% prevalence in those with AN (AN-BP = 18% vs. AN-R = 7%). Drug abuse/dependence disorders had a prevalence of 7% in AN (AN-BP = 9% vs. AN-R = 5%). In studies that looked at specific abuse/dependence disorders, there was a 10% prevalence of alcohol abuse/dependence in AN (AN-BP = 15% vs. AN-R = 3%) and a 6% prevalence of cannabis abuse/dependence (AN-BP = 4% vs. AN-R = 0%). In addition, in terms of substance use, there was a 37% prevalence for caffeine use, 29% prevalence for alcohol use, 25% for tobacco use, and 14% for cannabis use in individuals with AN. Conclusion This is the most comprehensive meta-analysis on the comorbid prevalence of SUDs and substance use in persons with AN, with an overall pooled prevalence of 16%. Comorbid SUDs, including drugs, alcohol, and cannabis, were all more common in AN-BP compared to AN-R throughout. Therefore, clinicians should be aware of the high prevalence of SUD comorbidity and substance use in individuals with AN. Finally, clinicians should consider screening for SUDs and integrating treatments that target SUDs in individuals with AN. Plain English Summary Individuals with anorexia nervosa (AN) may also present with substance use or have a substance use disorder (SUDs). Thus, we conducted a systematic review and meta-analysis to determine the prevalence of substance use and substance use disorders in individuals with AN. We examined published studies that reported the prevalence of either substance use or SUDs in individuals with AN. We found that substance use disorders had a 16% prevalence and that drug abuse/dependence disorders had a prevalence of 7% in those with AN. These rates were much higher in individuals with binge-eating/purging type compared to the restrictive AN. However, many specific substance use disorders and substance use types were low in individuals with AN. Nonetheless, clinicians should be aware of the high prevalence of SUD comorbidity and substance use in individuals with AN.