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Introduction Alcohol and cannabis use disorders are the most frequent comorbid substance use disorders (SUDs) among patients with eating disorders (EDs). EDs and SUDs involving alcohol and cannabis are independently associated with excess mortality. Objectives To investigate the impact of comorbid alcohol use disorder (AUD) and cannabis use disorder (CUD) on mortality in anorexia nervosa (AN), bulimia nervosa (BN), and unspecified eating disorder (USED) compared with matched control subjects. Methods This retrospective cohort study was conducted using Danish nationwide registers. The risk of mortality among ED patients with/without AUD and/or CUD was compared to matched control subjects with/without AUD and/or CUD using hazard ratios (HRs). Results Of the 20,759 included ED patients, 4.7% and 4.3% had AUD and CUD, respectively. The corresponding figures for the 83,036 control subjects were 1.0% (AUD) and 1.3% (CUD). ED patients without SUDs exhibited an increased risk of mortality compared to control subjects without SUDs (adjusted HR 2.9, P<.001). Mortality risk was higher among ED patients with AUD (adjusted HR 11.8, P<.001) or CUD (adjusted HR 4.6, P<.001) compared to control subjects without AUD/CUD. In addition, patients with AN, BN, and USED, who had comorbid AUD and/or CUD, exhibited an elevated risk of mortality compared to control subjects without AUD/CUD (AN: adjusted HR 11.3, P<.001; BN: adjusted HR 5.9, P<.001; USED: adjusted HR 10.9, P<.001). Conclusions Comorbid AUD and/or CUD increase mortality risk in patients with EDs. In order to reduce mortality in ED patients, prevention and treatment of AUD and CUD is important. Disclosure No significant relationships.