Background & Aims We analyzed the clinical factors associated with advanced liver fibrosis in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients. Methods We prospectively recruited treatment-naive HBeAg-positive patients for liver stiffness measurement (LSM) by transient elastography. Insignificant and advanced fibrosis was defined as an LSM of 6.0 kPa or less, and greater than 9.0 kPa for patients with alanine aminotransferase (ALT) levels less than or equal to the ƒ upper limit of normal (ULN), and 7.5 kPa or less and greater than 9.0 kPa for those with ALT levels between 1 and 5 × ULN, respectively, based on a previous study with histologic validation. Results A total of 453 patients were studied. Among 74 patients who also had a liver biopsy, the cut-off levels for advanced fibrosis had 95% specificity. Age and ALT level, but not hepatitis B virus DNA level, were associated independently with LSM. Based on receiver operating characteristics curve analysis, patients older than 35 years had the highest specificity for advanced fibrosis. The risk of advanced fibrosis increased in patients with an ALT level greater than 0.5 × ULN. Among the 47 patients who were older than 35 years with an ALT level of 0.5 × ULN or less, 39 (83%) had an LSM suggestive of insignificant fibrosis, and 1 (2%) had advanced fibrosis. Among the 217 patients who were older than 35 years with an ALT level greater than 0.5 × ULN, 61 (28%) had LSM indicating insignificant fibrosis, and 80 (37%) had advanced fibrosis. Conclusions Risk of advanced liver fibrosis increased in HBeAg-positive patients older than 35 years of age with an ALT level greater than 0.5 × ULN.