Background <p>Despite the high global vaccination coverage, the incidence of pertussis is rising in many countries. The epidemiological data on pertussis in children in the Xinjiang region are limited. This study aims to investigate the epidemiological characteristics of pertussis in this region, the protective effectiveness of vaccines, and the independent risk factors associated with the disease.</p> Methods <p>A retrospective study was conducted among 2,250 children with suspected pertussis who presented to the Pediatric Center of the First Affiliated Hospital of Xinjiang Medical University from March 2024 to June 2025. Children aged ≤ 18 years who met the suspected case criteria of the Chinese Guidelines for Diagnosis, Treatment and Prevention of Pertussis (2024 edition) and underwent nasopharyngeal PCR testing were included. Demographic, clinical, vaccination, and laboratory data were collected. <i>Bordetella pertussis</i> DNA was detected using a fluorescence probe-based PCR method. The χ² test was used to compare the differences between groups, and univariate and multivariate logistic regression analyses were used to identify independent risk factors.</p> Results <p>The overall positivity rate of pertussis was 9.3%. The positivity rate was the highest during the months of July to September. Moreover, the positivity rate was the highest in infants younger than 6 months (17.4% in 0–2 months and 16.2% in 3–5 months). The vaccination coverage was 90.3%; however, 82.9% of the positive cases had been vaccinated. Among children aged ≥ 3 months (eligible for vaccination), vaccine effectiveness (VE) against laboratory-confirmed pertussis was 47.1% (95% CI: 9.4–69.1%) for ≥ 1 dose versus unvaccinated. Multivariate analysis showed that age, season, history of cough contact, and laboratory markers (lymphocytosis) were independent predictors of pertussis positivity. In the age-restricted multivariable analysis (≥ 3 months, <i>n</i> = 1,741 complete cases), summer was the strongest risk factor (adjusted odds ratio [aOR] = 5.25, 95% confidence intervals [CI]: 3.27–8.45). History of cough contact (aOR = 2.54) and lymphocytosis &gt; 50% (aOR = 1.56) were significant risk factors. The age group of 1–2 years showed the strongest protective effect (aOR = 0.16, <i>p</i> = 0.006), reflecting a U-shaped age–risk curve.</p> Conclusions <p>In this single-center retrospective study of suspected pertussis cases in Xinjiang, children who tested positive were more likely to present in summer, have paroxysmal cough, and report a history of cough contact. Despite 90.3% vaccination coverage, the overall positivity rate was 9.3%, with a U-shaped age distribution peaking in infants aged 0–5 months and children ≥ 6 years. These findings highlight the potential value of maternal immunization strategies and timely booster vaccination, though multi-center prospective studies are needed to confirm these observations.</p> Trial registration <p>Not applicable.</p>