Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R 2 of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children.