The SHIELD program, a multicenter, multilevel intervention program in China, aimed to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The study included 30,109 pregnant women from 178 hospitals and 8,642 pregnant women from 160 community-level health facilities. The overall MTCT rate was 0.23% in the implementation stage and 0.23% in the community scale-up stage. Compliance with interventions significantly reduced the MTCT rate, from 3.16% among noncompliant participants to 0.16% and 0.03% in the hospital and community settings, respectively. The program integrated antenatal HBsAg screening, antiviral treatment for high-risk mothers, timely administration of the hepatitis B vaccine and immunoglobulin, and routine follow-up for exposed infants. The findings demonstrate the feasibility and effectiveness of comprehensive interventions in reducing HBV MTCT, with implications for global elimination efforts.The SHIELD program, a multicenter, multilevel intervention program in China, aimed to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The study included 30,109 pregnant women from 178 hospitals and 8,642 pregnant women from 160 community-level health facilities. The overall MTCT rate was 0.23% in the implementation stage and 0.23% in the community scale-up stage. Compliance with interventions significantly reduced the MTCT rate, from 3.16% among noncompliant participants to 0.16% and 0.03% in the hospital and community settings, respectively. The program integrated antenatal HBsAg screening, antiviral treatment for high-risk mothers, timely administration of the hepatitis B vaccine and immunoglobulin, and routine follow-up for exposed infants. The findings demonstrate the feasibility and effectiveness of comprehensive interventions in reducing HBV MTCT, with implications for global elimination efforts.