Serum HBsAg levels correlate with the duration of chronic HBV infection and may predict the extent of hepatic fibrosis.We analysed data from the SONIC-B database, which contains data from 8 global randomized trials and two large hepatology centers. Relationship between HBsAg levels and presence of significant fibrosis (Ishak 3-4) or cirrhosis (Ishak 5-6) were explored and clinically relevant cut-offs were identified to rule out cirrhosis.The dataset included 2779 patients; 1866 HBeAg-positive; 322 with cirrhosis. Among HBeAg-positive patients, lower HBsAg levels were associated with higher rates of significant fibrosis (Odds Ratio [OR] 0.419, P<0.001) and cirrhosis (OR 0.435, p<0.001). No relationship was observed among HBeAg-negative patients. Among HBeAg-positive patients, genotype specific HBsAg cut-offs had excellent NPVs (>97%) and low misclassification rates (≤7.1%) and may therefore have utility in ruling out cirrhosis. Diagnostic performance of the HBsAg cut-offs was comparable among patients in whom cirrhosis could not be ruled out with FIB-4.HBV genotype specific HBsAg cut-offs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C and D and can be an adjunct to FIB-4 to reduce the need for further testing.© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.