The objectives of this study were to assess the prevalence of personality disorders and to examine personality as a predictor of psychosocial characteristics and behaviors of HCV patients. HCV patients (n = 259) from three infectious disease and liver clinics who completed Cloninger’s Temperament and Character Inventory (TCI), an inventory for personality traits, were included in the study. Patients with low scale scores in the character dimension of both cooperativeness and self-directedness (low CO/SD) were defined as having a personality disorder. Using low CO/SD in combination with demographic, psychiatric/substance use, and HCV-related variables, linear regression was used to construct separate models of risky behaviors, quality of life, functioning, burden of illness, and social support. The prevalence of low CO/SD was high in this sample of HCV patients. Low CO/SD was an independent predictor of risky behaviors, quality of life, functioning, and social support.