ObjectiveThe objective of this survey was to describe epidemiological characteristics and evaluate vaccine effectiveness against pertussis in the sub-prefecture of Baoro (Central African Republic). MethodWe conducted a case control study from June to July 2022 in the sub-prefecture of Baoro in the district of Baour-Baoro. Community-based definitions of surveillance were applied to include cases and controls. ResultsAll in all, 143 confirmed and suspected cases and 166 controls were enrolled in this investigation. The epidemic had affected 12 neighborhoods and 9 villages. The village of Bugbassem alone had 32 patients, and 50% of the patients lived in rural areas. The age groups of 12 to 59 months accounted for 58% of cases. Patients were female in 54% of cases (p = 0.8). The attack rate among unvaccinated patients (65%) was higher than that of vaccinated patients (40%), while 15% (N = 21) of children were hospitalized with no recorded deaths. Pentavalent 3rd dose vaccination coverage was 49% in controls versus 33% in cases. Vaccination provided a significant protective effect (Odds Ratio = 0.3; 95% CI: 0.2–0.6). All told, vaccine efficacy against pertussis was 38%. ConclusionPertussis is a re-emerging disease currently occurring as a result of low pertussis vaccination coverage. It strongly affects rural areas with low vaccination rates. Vaccination strategy requires reinforcement in rural areas.