Spontaneous hepatitis B virus (HBV) e antigen (HBeAg) seroconversion is associated with reduced risk of liver‐related complications, but is poorly understood. In this study, 113 chronic hepatitis B patients in the immune active HBeAg‐positive phase were followed up for 76 weeks. Based on the outcome of liver function, HBeAg, hepatitis B viral e antibody (anti‐HBe) and HBV DNA at week 76, 18 patients were classified as spontaneous HBeAg seroconversion group (group A) and 95 patients were classified as non‐spontaneous HBeAg seroconversion group (group B). In multivariate logistic regression analysis, only week 28 HBV DNA levels were used for the logistic regression equation, and the odds ratio was 0.505 (95% confidence interval (CI): 0.366–0.697). The areas under the receiver operating characteristic curve for HBV DNA and HBeAg levels at week 28 were 0.824 (P < 0.001, 95% CI: 0.720–0.927) and 0.832 (P < 0.001, 95% CI: 0.744–0.921), respectively. Based on the maximization of Youden's index, the optimal cutoff values of HBV DNA and HBeAg levels at week 28 were 3.84 log10 IU/ml and 1.53 log10 PEI‐U/ml, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HBV DNA levels at week 28 were 50.0%, 97.9%, 81.8%, and 91.2%, respectively. The sensitivity, specificity, PPV, and NPV of HBeAg levels at week 28 were 94.4%, 60.0%, 30.9%, and 98.3%, respectively. In conclusion, the dynamic monitoring of HBV DNA and HBeAg levels predicted accurately determines spontaneous HBeAg seroconversion over the duration of 1 year. J. Med. Virol. 86:1838–1844, 2014. © 2014 Wiley Periodicals, Inc.