AIMS: Eating disorders (EDs) and substance use disorders (SUDs) often co-occur, and both involve somatic diseases. So far, no study has considered whether comorbid SUDs may impact somatic disease risk in patients with EDs. Therefore, this study aimed to examine the impact of comorbid SUDs on the risk of 11 somatic disease categories in patients with anorexia nervosa (AN), bulimia nervosa (BN) and unspecified eating disorder (USED) compared to matched controls. METHODS: A retrospective cohort study was conducted using Danish nationwide registries. The study population included 20 759 patients with EDs and 83 036 controls matched on month and year of birth, sex and ethnicity. Hazard ratios (HRs) were calculated to compare the risk of being diagnosed with a somatic disease (within 11 categories defined by the ICD-10) following first ED diagnosis (index date) between ED patients and controls both with and without SUDs (alcohol, cannabis or hard drugs). RESULTS: The ED cohort and matched controls were followed for 227 538 and 939 628 person-years, respectively. For ED patients with SUDs, the risk pattern for being diagnosed with different somatic diseases (relative to controls without SUDs) varied according to type of ED and SUD [adjusted HRs ranged from 0.95 (99% CI = 0.57; 1.59) to 4.17 (2.68, 6.47)]. The risk estimates observed among ED patients with SUDs were generally higher than those observed among ED patients without SUDs [adjusted HRs ranged from 1.08 (99% CI = 0.95, 1.22) to 2.56 (2.31, 2.84)]. Abuse of alcohol only had a non-synergistic effect on six disease categories in AN patients and five in BN and USED patients. Abuse of cannabis (with/without alcohol) had a non-synergistic effect on five disease categories in AN and BN patients and two in USED patients. Abuse of hard drugs (with/without alcohol or cannabis) had a non-synergistic effect on nine disease categories in AN patients, eight in BN patients and seven in USED patients. CONCLUSIONS: The present study documents non-synergistic but not synergistic harmful somatic consequences of SUDs among patients with different EDs, with AN and hard drugs being the most predominant factors. Hence, EDs and SUDs did not interact and result in greater somatic disease risk than that caused by the independent effects. Since EDs and SUDs have independent effects on many somatic diseases, it is important to monitor and treat ED patients for SUD comorbidity to prevent exacerbated physical damage in this vulnerable population.