GOALS: To determine the etiologies of chronic liver disease among American Indians. BACKGROUND: American Indians are disproportionately affected by chronic liver disease, yet little is known about its underlying etiologies in this group. STUDY: We conducted a cross-sectional prevalence study at medical centers serving American Indian populations in Arizona and California. Patients' records were reviewed to identify those with chronic liver disease (ICD-9 code for chronic liver disease or 2 abnormal liver tests > or = 6 mo apart). ICD-9 codes and laboratory findings were abstracted to determine etiologies. RESULTS: Of the 30,698 American Indian patients seen at the Arizona center during 2000 to 2002, 1496 (4.9%) had chronic liver disease, including 268/1496 (17.9%) with decompensated cirrhosis. Etiologies included alcohol (621; 41.5%), hepatitis C (103; 6.9%), both (136; 9.1%), or nonalcoholic fatty liver disease (191; 12.8%). Among alcohol-related liver disease patients tested for hepatitis C, 32.2% were positive. Of the 6074 American Indian patients seen at the California center during 2002 to 2003, 344 (5.7%) had chronic liver disease, including 45/344 (13.1%) with decompensated cirrhosis. Etiologies included alcohol (57; 16.6%) hepatitis C (83; 24.1%), and both (42; 12.2%). In one-third of chronic liver disease patient at the 2 centers, no etiology could be identified; 30% to 45% had not been tested for hepatitis C. CONCLUSIONS: Alcohol-related liver disease and hepatitis C were the most commonly identified etiologies among these American Indian patients with chronic liver disease in clinical care. Identifying American Indian and Alaska Native patients with chronic liver disease and providing treatment are critical for reducing disease burden.