Aim: Chronic persistent hepatitis B virus carriers are generally asymptomatic until the advanced stage of the disease. The “Hepatitis B-Carrier Clinics” of Chang Gung Memorial Hospital has been using alpha-fetoprotein (AFP) and liver ultrasound for early detection of hepatocellular carcinoma (HCC) in hepatitis B surface antigen (HBsAg) carriers since 1980.Methods: We evaluated the results of surveillance between 1980 and 2012 by collecting clinic data, matched cancer registry status, and national mortality database status. Results: Of 15,235 HBsAg carriers, 238 instances of HCC (1.5％ or 156.2/100,000 person-years) were detected over a mean follow-up period of 10.0 ± 7.6 years. There were more men (89.1％) and patients with liver cirrhosis (70.2％) in the HCC group (P < 0.001), and both the initial and maximal alanine aminotransferase (ALT) levels were higher in this group (P < 0.001). One hundred and thirty cases of HCC (54.6％) were identified during regular follow-up sessions, 55 (23.1％) were detected after the regular schedule had lapsed (“out-of-schedule”), and 53 (22.3％) were lost to follow-up completely. The mean tumor size was smaller in the regular group than in the out-of-schedule group (2.72 cm vs. 4.59 cm, P < 0.001), and the survival rate was higher (43.8％ vs. 30.9％, P < 0.001). Conclusion: The incidence of HCC was relatively low in the HBsAg-Carrier Clinics cohort. Surveillance for early diagnosis of HCC improved the survival of high-risk HBsAg carriers. To ensure cost-effectiveness, we suggest using different screening strategies according to the individual risk of hepatocarcinogenesis.