Background: Millions of Americans have hepatitis C and other liver diseases, many of whom have endstage osteoarthritis requiring total joint arthroplasty (TJA). This study aimed to determine the extent to which hepatitis C and other liver diseases are independent risk factors for complications, including readmission and reoperation, in patients undergoing TJA. Methods: Retrospective study of a REACHnet data set containing demographics, International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes, and clinical and laboratory data for patients who underwent primary total knee or hip replacement from 2013 to 2017 at 3 hospital systems in Louisiana and Texas. Multivariable logistic regression analyses examined predictors of complications. Any complication was defined as a 90-day medical complication or readmission or reoperation within 1 year. Results: Among 13,673 patients who met inclusion criteria, 14.9% (2044/13,673) had any complication, 11.7% (1600/13,673) were readmitted within 90 days, and 3.6% (497/13,673) had a reoperation within 1 year. Liver disease increased the odds for any complication (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.08-1.18), 90-day medical complication (OR, 1.13; 95% CI, 1.04-1.22), and 90-day readmission (OR, 1.11; 95% CI, 1.06-1.17). Hepatitis C was not, by itself, associated with an increase in any type of complication but was usually associated with liver disease. Comorbidity severity was the strongest predictor of all types of complications after TJA. Conclusion: Patients in Louisiana and Texas with liver disease were at increased risk for complications after TJA, corroborating findings of previous studies. Hepatitis C was not an independent predictor of complications because of its high association with liver disease.