It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32% and 41% respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a significantly decreased local disease-free survival (LDFS) was seen in HBV-positive (5-year LDFS 26%) or HCV-positive (5-year LDFS 38%) patients compared to those with negative serology (5-year LDFS 79%; P <0.05). There was also a trend toward a decreased overall survival in patients with positive hepatitis serology compared to patients with negative serology (37% vs. 79%; P = 0.12). Univariate analysis revealed that only satellitosis was related to local recurrence and overall survival. Patients with positive serology for hepatitis B or C undergoing resection for hepatocellular carcinoma have a trend toward worse overall prognosis and a significantly decreased LDFS when compared to patients with negative serology.