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Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a syndrome involving multiple systems. Liver injury is the most common visceral manifestation. Objective The purpose of this study was to investigate the types of liver injury and factors associated with DRESS. Methods A retrospective cohort study was conducted in Taiwan using a DRESS database compiled from December 2000 to March 2013. Results Seventy-two cases were included in this study. Among them, 62 (86.1%) cases involved liver injury, 6 of which (9.7%) were liver injury before skin presentation. The distribution of liver injury patterns at initial presentation was 23 cholestatic type (37.1%), 17 mixed type (27.4%), and 12 hepatocellular type (19.4%). Patients with hepatocellular-type injuries were younger, with a median age of 31.5 ( P = .044). Individuals with liver function results more than 10 times the upper limit were more likely to have fever ( P = .026), took more time to recover, and had fewer eosinophils in the dermis ( P = .002). Limitations The study was a retrospective cohort study with limited cases. Conclusions Liver injury is common in DRESS and frequently associated with atypical lymphocytosis. The cholestatic type is the most common type. Patients with cholestatic-type injuries were older and more frequently had interface changes in skin pathology.