Background The study aimed to investigate the effects of accident pregnancy CHB (Chronic Hepatitis B) patients’ reproductive age on their offspring during entecavir (ETV) antiviral therapy. Methods We retrospectively enrolled 112 couples were divided into observational and control groups. 53 couples who had accident pregnancies while receiving long-term ETV antiviral medication were recruited for the observational group. The control group comprised 59 couples who became pregnant accidentally while receiving long-term TDF antiviral treatment. All mothers persisted in their pregnancies in the observational group, and ETV was promptly replaced with TDF. Every mother remained pregnant and continued to use TDF in the control group. Results The maternal and baby safety profiles, including the prevalence of congenital disabilities, were comparable across the observational and control groups at delivery. In addition, no unusual indications or symptoms of the newborns were noted during the follow-up intervals of 28, 48, and 96 weeks postpartum. Conclusions Initiating ETV or TDF in early and middle pregnancy seems to be safe for both mothers and infants. Important data from our investigation support using ETV in early-mid gestational accident pregnancies and the prompt substitution of TDF antiviral medication for ETV. The pregnancy was not needed to be terminated.