Comprehensive clinical and standardized histologic descriptions of horses with naturally occurring hepatic disease in the western United States have not been performed. The purpose of this study was to describe clinical and histologic features of horses with hepatic disease admitted to a referral hospital in the western United States. A retrospective case review of 92 horses of various breeds residing in the western United States older than 1 year of age admitted between 2000 and 2010 with liver disease confirmed by histopathology was performed. Clinical data were retrieved from the medical record. Slides were reviewed, with a standardized hepatic histologic evaluation by a single board certified veterinary pathologist. Case follow-up information was obtained through phone interview. Sex was evenly distributed, and median age was 10 years (range, 1–31 years). Portal inflammation, portal fibrosis, necrosis, and lipidosis were commonly observed, and the majority of horses had moderate to severe grades of histologic injury. Sixty-eight horses were euthanized, and 24 were discharged from the hospital, with follow-up available for 19 obtained through phone interview. Six horses (32%) were euthanized within 1 year of hospital discharge, three from progression of primary liver disease, and three from colic. Hepatic disease in horses in the western United States often has serious consequences, with severe illness and often death of as a clinical outcome.