Byline: H. Jensie Burton, From the Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, Charleston, the Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, and the Department of Biomedical Informatics, Ohio State University, Columbus.; Aastha Khatiwada; Dongjun Chung; Eric G. Meissner Abstract OBJECTIVES: Therapeutic advances make the cure of chronic hepatitis C virus (HCV) infection achievable for individuals aware of their diagnosis who can access care. Identifying barriers to accessing care is critical to achieve population-level HCV elimination and improve the cascade of care from diagnosis to cure. METHODS: To identify barriers to HCV care, we performed a retrospective observational analysis of outcomes for patients with chronic HCV referred to an infectious diseases clinic at an academic medical center in Charleston, South Carolina between January 1, 2015 and January 1, 2020. We categorized outcomes in the cascade of care between "never presenting for evaluation" and "completed treatment with documented cure." Patient demographic factors, referral source, ZIP code of residence, insurance status, clinical characteristics, antiviral regimen, psychiatric and substance use history, and route of infection were assessed for associations with care outcomes. RESULTS: Of 407 referrals, 32% of patients never presented for an initial evaluation, an outcome that was associated with active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider. Of the patients who presented for an initial evaluation, 78% of patients initiated treatment. Active substance use was the only variable associated with lack of therapy initiation after presenting for an initial evaluation (odds ratio 2.5, 95% confidence interval 1.07-5.84). Once treatment had been initiated, no clinical or demographic variables were associated with odds of achieving documented or presumed HCV cure. CONCLUSIONS: Active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider were associated with a lower odds of presenting for evaluation and initiation of HCV treatment. Innovative models to improve access to care and increase outreach to vulnerable populations will be essential to eliminate HCV.