A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Master’s in Life Sciences of the Nelson Mandela African Institution Sciences and TechnologyInfectious bursal disease (IBD) is a viral infection that affects young chicks. The IBD outbreaks in vaccinated chickens are frequently reported in Tanzania. The current study was conducted to determine the possible causes of vaccination failure focusing on knowledge, attitude and practices (KAPs) of vaccine sellers and poultry farmers, maternally derived antibodies (MDA), immunogenic potential of Virgo 7 vaccine and the phylogenetic relationship between the vaccine and the field strains. A cross-sectional study was performed to gather information on KAPs from 384 farmers and 20 veterinary outlets in Dar es Salaam. Results revealed inadequate knowledge of farmers in IBD management and breaches in the cold chain maintenance by vaccine sellers. 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, this confirming its immunogenic efficacy. Isolated nucleic acids from the vaccine and field strains were sequenced and result shows that 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 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 seller 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.