© Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. Background. Hepatitis C virus (HCV) testing guidance issued by the Centers for Disease Control and Prevention in 1998 recommends HCV antibody (anti-HCV) testing for persons with specified risk factors. The purpose of this study was to determine the prevalence and predictors of anti-HCV positivity among primary care outpatients and estimate the proportion of unidentified anti-HCV-positive (anti-HCV +) persons using risk-based testing. Methods. We analyzed electronic medical record data from a 4-site retrospective study. Patients were aged ≥ 18 years, utilized ≥ 1 outpatient primary care service(s) between 2005 and 2010, and had no documented evidence of prior HCV diagnosis. Among persons tested for anti-HCV, we fit a multilevel logistic regression model to identify patient-level independent predictors of anti-HCV positivity. We estimated the proportion of unidentified anti-HCV + persons by using multiple imputation to assign anti-HCV results to untested patients. Results. We observed 209 076 patients for a median of 5 months (interquartile range, 1-23 months). Among 17 464 (8.4%) patients who were tested for anti-HCV, 6.4% (n = 1115) were positive. We identified history of injection drug use (adjusted odds ratio [95% confidence interval], 6.3 [5.2-7.6]), 1945-1965 birth cohort (4.4 [3.8-5.1]), and elevated alanine aminotransferase levels (4.8 [4.2-5.6]) as independently associated with anti-HCV positivity. We estimated that 81.5% (n = 4890/6005) of anti-HCV + patients were unidentified using risk-based testing. Conclusions. In these outpatient primary care settings, risk-based testing may have missed 4 of 5 newly enrolled patients who are anti-HCV +. Without knowing their status, unidentified anti-HCV + persons cannot receive further clinical evaluation or antiviral treatment, and are unlikely to benefit from secondary prevention recommendations to limit disease progression and mortality.