This research article Journal of Veterinary Medicine and Animal Health, Vol. 12(3), July-September 2020Infectious bursal disease (IBD) is a viral infection that affects young chicks. The IBD outbreaks in vaccinated chickens are reported in Tanzania frequently. The current study was conducted to find out the possible causes of vaccination failure focusing on knowledge and practices of vaccine sellers and users, the immunogenic potential of currently used vaccine and the phylogenetic relationship between the vaccine and the field strains. A cross-sectional study was performed to gather information on knowledge and practices from 384 poultry farmers and 20 veterinary outlets in Dar es Salaam. Results revealed inadequate knowledge of farmers in vaccine handling and administration and also breaches in the cold chain maintenance by vaccine sellers was apparent. A total of 60 chicks were experimentally vaccinated with Virgo 7 strain vaccine and titers of induced antibodies assessed. The vaccine induced adequate antibodies against IBDV, confirming its immunogenic efficacy. Isolated nucleic acids from the vaccine and field strains were sequenced and result shows that IBDV field isolates, are genetically different from the vaccine strains used in the country. The field isolates belong to the vvIBDV African types, while the vaccines belong to the vvIBDV European/Asian or classical virulent types. Putting together results from this study reveals multiple possible reasons which may contribute to vaccine failures. These include poor vaccine handling by farmers and vaccine sellers and the genetic disparity between the field and vaccine strains. It is therefore recommended that veterinary regulatory authorities should ensure good vaccine handling practices and considering local virus isolates during vaccine development.