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Newcastle disease (ND) is endemic in traditional poultry farming in Burkina Faso. Despite government's efforts, international organizations and farmer associations in supporting vaccination campaigns, the use of vaccines by farmers remains limited. A cross-sectional survey was carried out from August to September 2023 to understand the determinants of ND vaccination uptake in the commune of Boussouma (Kuilsé region of Burkina Faso). Structured interviews were conducted with 483 households keeping chickens from 23 villages. Descriptive statistics and multivariate logistic regression were carried out to identify the factors that influence the uptake of ND vaccines by farmers. Farmers with less experience in chicken rearing (less than 10 years of experience) were more likely to adopt vaccine than others (equal or more than 10 years of experience) (OR: 6.86; CI: 2.38–19.76; p = 0.001). Similarly, farmers who kept pullets (OR: 4.24; CI: 1.74–10.35; p = 0.002) and roosters (OR: 3.86; CI: 1.76–8.46; p = 0.001) were more likely to adopt vaccination than those who did not. The lack of sensitization of farmers regarding ND disease was negatively associated with vaccine uptake (OR: 0.004; CI: 0.00–0.04; p = 0.001). Farmers who previously experienced ND in their flocks tended to have lower vaccine uptake than those who did not (OR: 0.37; CI: 0.16–0.85; p = 0.019). Biosecurity practices such as regular cleaning of the chicken house (OR: 4.46; CI: 2.17–9.16; p = 0.001) were associated with vaccine uptake, whereas disposal of dead chickens was not (OR: 0.23; CI: 0.11–0.49; p = 0.001). Sourcing poultry health services from community animal health workers (CAHWs) was positively associated with vaccine uptake (OR: 6.00; CI: 3.06–11.77; p = 0.001), whereas sourcing the same services from village poultry traders was not (OR: 0.23; CI: 0.08–0.68; p = 0.008). The findings emphasize the crucial role of farmer experience, flock structure, hygiene and the importance of health advice from CAHWs towards the uptake of vaccines against ND in chickens. To improve farmers uptake of ND vaccines, it is essential to increase awareness among farmers about the disease, build their understanding on the importance of and trust in vaccination, strengthen biosecurity measures within chicken flocks, and facilitate farmer's access to quality local animal health services through CAHWs.