We studied the hepatitis B virus (HBV)-DNA levels below which the development of cirrhosis-related complications became unlikely in chronic hepatitis B (CHB). Seventy-nine Chinese CHB patients with cirrhosis-related complications and 158 age-, sex- and HBeAg status-matched patients without complications were enrolled. The precore and core promoter mutations were detected by the Line Probe assay (LiPA). HBVDNA levels were determined by Digene assay and Cobas Amplicor Monitor test. Patients with complications had higher HBVDNA levels than those without complications (P = 0.02). HBeAg-positive patients with complications had similar alanine transferase (ALT) and HBVDNA levels and frequency of precore mutations, but higher frequency of core promoter mutations (P = 0.003), compared with those without complications. Anti-HBe-positive patients with complications had higher ALT and HBVDNA levels (P < 0.01) but similar frequency of precore and core promoter mutations, compared with those without complications. Anti-HBe patients (24.5%) with complications had HBVDNA levels <10(4) copies/mL. The major factor for the development of cirrhotic complications was viral loads but cirrhotic complications continued to develop in patients with HBVDNA levels below 10(4) copies/mL.