Abstract:Abstract OBJECTIVE: To systematically analyse reports of adverse reactions to the nine-valent HPV vaccine (Gardasil9) in the US VAERS database and assess its safety profile. METHODS: By searching the VAERS database, the reported data related to the nine-valent HPV vaccine from 2015 to 2023 were extracted, and descriptive statistics and signal mining methods (e.g., ratio of reported ratios, ROR) were used to analyse the types of adverse reactions, their severity, and the characteristics of the population. RESULTS: A total of 11,230 reports were included, with the most common adverse events being dizziness (1,340), syncope (1,250), and headache (962); the proportion of serious adverse events was 12.6%. Adolescents (9-17 years old) and females were the high reporting groups. Adverse reactions were most likely to occur during the first dose of vaccination. CONCLUSION: The overall safety of the nine-valent HPV vaccine is manageable, but risk management of acute reactions, such as syncope, needs to be addressed.The spontaneous reporting nature of the VAERS data may lead to bias and needs to be further validated in conjunction with active surveillance studies.