Objectives: To investigate the variability in liver stiffness (LS), measured by transient elastography, and determine the possible influencing factors in hepatitis B virus infection. Methods: This cross-sectional study was conducted at the Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China from March to June 2010. Three successful measurements at different sites in 123 patients were obtained, and the LS discrepancy was calculated. The influence of clinical data on the discrepancy was also assessed. Results: The LS discrepancy was 1.3 (0.2-16.5) kPa and independently increased with a fibrosis stage: 0.9 (0.2-4.4) kPa in F0/F1, 1.5 (0.4-3.7) kPa in F2, 3.0 (0.3-9.4) kPa in F3, and 7.4 (3.1-16.5) kPa in F4. A discrepancy >= 2 kPa was observed in 45 (36.6%) patients: 8 (11.9%) with F0/F1, 7 (31.8%) with F2, 15 (73.7%) with F3, and 15 (100%) with F4. The incidence of discrepancy >= 2 kPa was only associated with fibrosis stage in multiple regression analysis. Discordance in fibrosis stages was observed in 33 (26.8%) patients, and was most frequent in stage F2 (F0/F1, 10.45%; F2, 68.2%; F3, 36.8%; and F4, 26.7%). Conclusion: The LS discrepancy is common and associated with fibrosis stage independently. While determining the fibrosis stage and disease progression, LS discrepancy should be considered.