The present study aimed to investigate the effects of accidental pregnancy CHB patients' reproductive age on their offspring during entecavir (ETV) antiviral therapy. A total of 112 couples were retrospectively enrolled, and they were divided into an observational and control group. A total of 53 couples who had accidental pregnancies while receiving long-term ETV antiviral medication were recruited for the observational group. The control group consisted of 59 couples who became pregnant accidentally while receiving long-term tenofovir disoproxil fumarate (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. 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. Initiating ETV or TDF in early and middle pregnancy seems safe for mothers and infants. Important data from the present study support using ETV in early-mid gestational accidental pregnancies and the prompt substitution of TDF antiviral medication for ETV.