The race of patients infected with hepatitis C virus (HCV) in the United States may be associated with the risk for cirrhosis and hepatocellular carcinoma (HCC). However, previous studies are too small to provide convincing data regarding the effect of race on cirrhosis and HCC risk after accounting for demographic, clinical, and virological factors. We used the Veterans Administration (VA) HCV Clinical Case Registry to identify patients with confirmed viremia between 2000 and 2009 and with at least 1 year of follow-up in the VA. We identified cirrhosis and HCC cases through early 2010. Cox proportional hazard regression models were performed to examine the effect of race on the risk for cirrhosis and HCC while adjusting for patients' age, gender, period of service (World War I/II, Vietnam era, post-Vietnam era), HIV coinfection, HBV coinfection, alcohol abuse, diabetes, body mass index, and antiviral treatment receipt and response. There were 149,407 patients with active HCV viremia. Of them, 56.3% were non-Hispanic White (NHW), 36.1% were African American (AA), 6.0% were Hispanic, and 1.6% belonged to other racial groups. After an average follow-up of 5.2 years, 13,099 patients were seen to have a recorded diagnosis of cirrhosis and 3,551 had HCC. Hispanics had the highest annual incidence rates of cirrhosis and HCC (28.8 and 7.8%, respectively), whereas AAs had the lowest rates (13.3% and 3.9%, respectively) compared with NHWs (21.6 and 4.7%, respectively). There were differences among NHW, AA, and Hispanic patients in the rates of HIV infection (2.1, 2.5, and 6.0%, respectively), HCV genotype 1 (50.0, 50.6, and 64.2%, respectively), obesity (28.0, 25.4, and 30.9%, respectively), diabetes (8.7, 16.1, and 16.1%, respectively), and absence of antiviral treatment (81.1, 89.6, and 82.1%, respectively). However, adjusting for differences in demographic and clinical factors did not change the magnitude or direction of the race effect. Compared with NHWs, Hispanic patients had a higher risk of having cirrhosis recorded (adjusted hazard ratio (HR)=1.28, 95% confidence interval (CI)=1.21-1.37) and HCC (1.61, 95% CI=1.44-1.80). In contrast, AAs had a lower risk of cirrhosis (HR=0.58, 95% CI=0.55-0.60) and HCC (0.77, 95% CI=0.71-0.83) compared with NHWs. Hispanics with HCV are at a significantly higher risk, whereas AAs are at a considerably lower risk of developing cirrhosis and HCC than are NHWs. These associations persisted even after adjusting for a range of factors including HCV genotype, HCV treatment, diabetes, and body mass index.