GOALS: To determine the outcomes of implementing clinical care guidelines for Hepatitis C screening, evaluation, and treatment in a large urban Veterans Affairs Medical Center. BACKGROUND: Little information exists regarding the actual outcomes of institutional screening programs for Hepatitis C. STUDY: Retrospective review of all patients tested for Hepatitis C at the Minneapolis Veterans Affairs Medical Center from January 1, 2000 to December 31, 2001. Logistic regression was used to determine factors related to successful referral and treatment. RESULTS: During this period 36,422 unique patients were screened for Hepatitis C virus (HCV) risk factors, resulting in 12,485 HCV enzyme-linked immunoassay antibody tests. HCV antibodies were positive in 681 (5.4%) patients and 520 (4.2%) were HCV-RNA-positive. Of HCV-RNA-positive patients, 430 (83%) were referred, 382 (73%) attended the Hepatitis clinic, and 232 (44.6%) received liver biopsies. Patients referred had significantly fewer comorbidities, known marital status, and greater prior clinic attendance than those not referred. Overall, 124 patients with established fibrosis received antiviral therapy (32% of patients attending clinic or 24% of viremic cohort). White race, fewer major medical problems, and age less than 60 years predicted antiviral treatment. Sustained virologic response occurred in 46 (37%) of treated patients (9% of the viremic cohort). Patients with a sustained virologic response include 17 patients with stage 3 to 4 fibrosis. CONCLUSIONS: This screening and referral program resulted in 73% of HCV-RNA-positive patients attending a specialty Hepatitis C clinic and 24% of those most likely to benefit received antiviral therapy. Measures to increase referral, engagement in care, and antiviral treatment are needed.