Purpose : Women of childbearing age may receive HPV vaccination during pregnancy, yet evidence on birth defects (BDs) risks remains limited. This study evaluates associations between peri-conception HPV vaccination and BDs. Methods: This population-based retrospective cohort study included pregnancies conceived between March 2018 and December 2021 in Xiamen, China. Propensity score matching based Poisson regression was used to estimate the adjusted relative risk (aRR) of exposure for total BDs and 10 organ system-specific BDs. Two subgroup analyses, including different exposure windows and vaccine valences, six sensitivity analyses, and a negative control analysis were performed. Results: A total of 177,574 pregnancies were included, of which 566 were exposed to the HPV vaccine during the Peri-conception period. The rate of Peri-conception vaccine exposure increased from 0.10% in 2018 to 0.58% in 2021. After 1:4 PSM, peri-conception HPV vaccination was not associated with an increased risk of total BDs (aRR 0.77, 95% confidence interval [CI] 0.42-1.42). Similarly, no significant association was found between HPV vaccination and the risk of 10 organ system-specific BDs. In subgroup analyses, exposure during pre-30 days (aRR 0.59, 95%CI 0.23-1.48) and the first trimester (aRR 0.61, 95%CI 0.14-2.69), exposure to the 4vHPV (aRR 1.25, 95%CI 0.62-2.51) and 9vHPV (aRR 0.57, 95%CI 0.13-2.49) vaccines were not associated with a higher risk of total BDs. All sensitivity and negative control analyses demonstrated the robustness of the results. Conclusions: Our evidence suggests that exposure to the HPV vaccine before and during early pregnancy does not increase the risk of birth defects. This conclusion helps increase the willingness of women of childbearing age to receive HPV vaccination. Trial registration: This study was registered at ClinicalTrials.gov (NCT06180447).