BACKGROUND: Interstitial lung diseases (ILDs) are associated with a high burden of disease. However, data on the prognostic impact of comorbidities and comorbidity-related pharmaceutical treatments in patients with various ILDs remain sparse. METHODS: Using longitudinal claims data from a German Statutory Health Insurance Fund, we assessed comorbidity in ILD subtypes and associated drug treatments. Baseline comorbidity was assessed via the Elixhauser Comorbidity Index that was amended by ILD-relevant conditions. Drug treatment was assessed on the substance level using the ATC-codes of drugs prescribed at the time of ILD diagnosis. Subsequently, the comorbid conditions (main analysis) and pharmaceutical substances (secondary analysis) with a meaningful association to survival were identified for the complete ILD cohort and within the subtype strata. For this, we applied multivariate Cox models using a LASSO selection process and visualized the findings within comorbidomes. RESULTS: In the 36,821 patients with ILDs, chronic obstructive pulmonary disease (COPD), arterial hypertension, and ischaemic heart disease (IHD) were the most prevalent comorbidities. The majority of patients with cardiovascular diseases received pharmaceutical treatment, while, in other relevant comorbidities, treatment quotas were low (COPD 46%, gastro-oesophageal reflux disease 65%). Comorbidities had a clinically meaningful detrimental effect on survival that tended to be more pronounced in the case of untreated conditions (e.g. hazard ratios for treated IHD 0.97 vs. 1.33 for untreated IHD). Moreover, comorbidity impact varied substantially between distinct subtypes. CONCLUSIONS: Our analyses suggest that comorbid conditions and their treatment profile significantly affect mortality in various ILDs. Therefore, comprehensive comorbidity assessment and management remains important in any ILD.