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Background and Aims Chronic hepatitis B ( CHB) can progress to cirrhosis, hepatocellular carcinoma ( HCC), and ultimately liver-related deaths. Recently, owing to potent antiviral therapy with minimal side-effects, sustained suppression of hepatitis B virus replication can be achieved, thereby preventing such complications. We aimed to reappraise clinical courses regarding disease progression in the era of antiviral therapy. Methods Between 2001 and 2005, treatment-naïve Korean CHB patients without cirrhosis were enrolled and followed up for at least 5 years. During follow up, antiviral therapy was commenced according to Korean Association for the Study of the Liver guidelines, if eligible, and ultrasonography and laboratory and clinical assessment were performed regularly. Primary end-points were development of cirrhosis, hepatic decompensation, HCC, or liver-related deaths. Results Of 360 patients, 323 (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%), or telbivudine (6.5%). During follow up, cirrhosis developed in 29 (8.1%), hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and 0.53% per person-year, respectively. Age was an independent predictor for developing cirrhosis (hazard ratio [ HR] 1.075, 95% confidence interval [ CI] 1.037-1.116; P < 0.001), whereas age ( HR 1.060, 95% CI 1.012-1.111; P = 0.014) and cirrhosis ( HR 17.470, 95% CI 5.081-60.063; P < 0.001) were those for developing HCC. Conclusions In the era of antiviral therapy, overall clinical courses have been much improved since introduction of lamivudine in 1999. However, patients with older age or cirrhosis are still subject to HCC development despite appropriate antiviral therapy, necessitating cautious surveillance. [ABSTRACT FROM AUTHOR]