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Introduction: Patients with cirrhosis are at risk for adverse drug reactions (ADRs) due to altered pharmacokinetics and pharmacodynamics. We aimed to determine the prevalence of drug prescriptions and the potential safety of these prescriptions in a real-world cohort of patients with cirrhosis. Methods: This was a retrospective cohort study based on linked real-world data from the Out-patient Pharmacy Database and the Hospitalisation Database of the PHARMO Database Network. Patients with a diagnosis of cirrhosis between January 1998 and December 2015 were included. Follow-up ended when the patient underwent a liver transplant, died, transferred out of the database, or on 31 December 2015. Prescription data were derived from a community pharmacy database and were compared with our previously developed safety recommendations for 209 drugs. Results: In total, 5618 patients were included and followed for a median of 3 years (interquartile range [IQR] 1–7). In the first year after the diagnosis, patients used a median of nine drugs (IQR 5–14), with proton pump inhibitors (prevalence 53.9%), aldosterone antagonists (43.6%), and sulfonamide diuretics (41.3%) being the most commonly used drug groups. Almost half (48.3%) of 102,927 prescripti