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• A test-negative case-control study examined an effectiveness of pertussis vaccine. • 4 doses of vaccine provided a high effectiveness in subjects under 6 years of age. • Vaccine effectiveness declines with time passed since the fourth dose. • 4 doses of pertussis vaccine have no preventive effect for school-aged children. The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6–12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program. Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis. Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0–8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01). Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis. [ABSTRACT FROM AUTHOR]