ABSTRACT Background: Real-world evidence on the effectiveness of COVID-19 vaccines marketed in China against the Omicron BA.2 variant remains scarce. Methods: A case-control study was conducted to estimate the vaccine effectiveness (VE) of COVID-19 vaccines marketed in China, including inactivated vaccines, an Ad5-nCoV vaccine, and a recombinant protein vaccine. The study included 414 participants infected with SARS-CoV-2 as cases and 828 individuals in close contact with COVID-19 patients as controls during the outbreak of the Omicron variant in April 2022 in Lu’an City, Anhui Province, China. Controls were selected from core close contacts based on a random sampling method with consecutive negative test results. Each case corresponded to two controls. Results: A total of 414 cases and 828 controls were included in this study. Compared to unvaccinated participants, the overall VE against Omicron BA.2 variant infection in the vaccinated group with any COVID-19 vaccine was 35.0% (95% CI: −9.1–61.3%), whereas the VE for booster vaccination was 51.6% (95% CI: 15.2–72.4%). Subgroup analysis showed that the overall VE of the Ad5-nCoV vaccine (65.8%, 95% CI: 12.8–86.6%) during the outbreak was higher than that of the inactivated vaccine (35.5%, 95%CI:-8.6–61.7%) and recombinant protein vaccine (13.0%, 95%CI:-76.1–57%). COVID-19 vaccines offered 46.8% (95% CI: 9.5–68.7%) protection for infection within 6 months, and no protection after 6 months. The VE of heterologous booster vaccination (76.4%, 95% CI: 14.3–93.5%) was considerably higher than that of homologous booster vaccination (51.8%, 95% CI: 9.6–74.3%). Conclusion: Booster vaccination of COVID-19 vaccines marketed in China offered more protection than full vaccination. A booster vaccination campaign for a booster dose after three doses of a recombinant protein vaccine must be urgently conducted. Keywords COVID-19 vaccines; Omicron; vaccine effectiveness; inactivated vaccine; Ad5-nCoV vaccine; recombinant protein vaccine