Background/Aims: Prior studies have demonstrated neuropsychological abnormalities in chronic hepatitis C (CHC) patients even with mild fibrosis. The aim of this study was to determine the frequency, type, and severity of cognitive impairment in a large group of CHC patients with advanced fibrosis. Methods: Ten validated neuropsychological tests were administered to 201 CHC patients. Standard scores for individual tests were calculated using normative population data that controlled for age, gender, and/or education. Lifetime psychiatric history, alcohol consumption, and mood status were also determined. Results: 33% of patients met criteria for cognitive impairment (i.e. standard score < 40 on at least 4 tests). Mild impairment in verbal recall and working memory were noted with other domains remaining intact. Liver disease severity and lifetime psychiatric/substance abuse history did not correlate with group mean cognitive test results or the presence of cognitive impairment. In contrast, IQ and depression scores were significant and independent predictors of cognitive impairment (ROC=0.84) . Conclusions: 33% of patients entering the HALT-C trial have evidence of a mild, non-focal subcortical processing deficit which was highly correlated with IQ, education, and occupation. Future studies of cognitive function in CHC patients should control for general cognitive ability. Background / Aims: Prior studies have demonstrated neuropsychological abnormalities in chronic hepatitis C (CHC) patients even with mild fibrosis. The aim of this study was to determine the frequency, type, and severity of cognitive impairment in a large group of CHC patients with advanced Methods: Ten validated neuropsychological tests were administered to 201 CHC patients. Standard scores for individual tests were calculated using normative population data that controlled for age, gender, and / or education. Lifetime psychiatric history, alcohol consumption, and mood status were also Mild impairment in verbal recall and working memory were noted with other domains remaining intact. Liver disease severity and lifetime psychiatric / substance abuse history did not correlate with group mean cognitive test results or the presence of cognitive impairment. In contr ast, IQ and depression scores were significant and independent predictors of cognitive impairment (ROC = 0.84). Conclusions: 33% of patients entering the HALT-C trial have evidence of a mild, non-focal subcortical processing deficit which was highly correlated with IQ , education, and occupation. Future studies of cognitive function in CHC patients should control for general cognitive ability.