Serum levels of hepatitis B virus (HBV) DNA ( £ 2000 IU/mL) and hepatitis B surface antigen (HBsAg) (<1000 IU/mL) have been shown to distinguish inactive carriers with high accuracy. The goal of this study was to validate the predictability of onetime measurement of quantitative HBsAg and HBV DNA levels for inactive carrier status and chronic hepatitis B (CHB) progression in a community-based cohort. This study included 1529 participants chronically infected with HBV genotype B or C from the REVEAL-HBV cohort. They were ascertained as inactive or active CHB after 18 months of follow-up. Validity of the one-time measurement was assessed by sensitivity, specificity, and receiver operating characteristic curves, while associations with clinical outcomes were calculated with Cox proportional hazards regressions. The one-time baseline measurement of HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL distinguished inactive carriers from active CHB with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 71%, 85%, 83%, 74%, and 78%, respectively. Those identified as inactive carriers using the one-time baseline measurement had multivariate adjusted hazard ratios of 0.36 (95% confidence interval [CI], 0.20-0.63) and 0.36 (0.23-0.56) for hepatocellular carcinoma and liver cirrhosis, respectively, and an adjusted rate ratio of 6.97 (95% CI, 5.21-9.33) for HBsAg seroclearance. Areas under the receiver operating characteristic curve of predicting these outcomes using the one-time definition were similar to those obtained when using long-term follow-up defined carrier status for prediction. Conclusion: This study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for future inactive carriers. This single-point strategy provides new and complementary information useful for management of patients with chronic hepatitis B infection. (HEPATOLOGY 2016;64:381-389) C hronic hepatitis B (CHB) infection is a large global health problem due to its widespread geographical prevalence and its varying clinical consequences, which range from inflammation and infection to liver cirrhosis and hepatocellular carcinoma (HCC).(1) The characterization of patients with CHB is often divided into hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. It is well-known that HBeAg-seropositive patients are at increased risk for HCC, and HBeAg seroconversion is an important milestone for clinical management of these patients.(2,3) On the other hand, HBeAg-negative patients can be defined clinically as inactive carriers or as patients with active CHB. Inactive carriers typically have HBV DNA levels <2,000 IU/mL and normal alanine aminotransferase (ALT) levels, whereas those with active CHB have HBV DNA levels >2,000 IU/mL with fluctuations that reach >20,000 IU/mL in some patients, accompanied by intermittent or persistent ALT elevation. (2,4) Previous studies have shown that compared with individuals with active CHB, inactive carriers have a significantly bett...