The objectives of this study were to define the prevalence of intrafamilial transmission of HCV and evaluate the risk factors in this setting. A cross-sectional, family-based seroepidemiological study was performed in Cairo Liver Center and Oncology Diagnostic Unit, Ain Shams University. A total of 102 index patients (72 males and 30 females) with type C chronic liver disease and their 305 family contacts were studied. Only 265 family contacts were eligible for the study as they showed no previous history of exposure to risk factors. Overall, 15 family contacts (5.7%) were positive for anti-HCV, indicating a lower anti-HCV prevalence among family contacts than the general population in Egypt. Spouses were at higher risk of infection (16.7%) than family members (2.6%). Among the repeatedly positive samples for anti-HCV, only 3 samples were HCV-RNA positive (1.1%), all were spouses. Logistic regression analysis revealed that spouses reporting promiscuous sexual relations were at higher risk than those with normal sexual relations. Contacts sharing personal objects were also at higher risk to develop HCV infection. Index cases reporting previous blood transfusion (18.6%), i.v. antibilharzial therapy (33.3%), multiple sex partners (1.0%) or advanced liver diseases were more infective to their family contacts. The contacts of index cases had increasing risk of HCV infection with increase in age and duration of contact. The prevalence rate of intrafamilial spread of HCV infection is low compared to the rate among general population, emphasizing its limited role in transmitting HCV infection. Long duration of sexual contact and promiscuous sexual activities were major risk factors in this setting.