Newcastle disease is the major constraint to village poultry production in the world but more so in developing countries. Eradication of this disease is unlikely but it can be effectively controlled through vaccination. This study was conducted in Iganga district in Bulyansiime and Kikunu villages, purposively selected because of their high level of poultry activity, prevalence of Newcastle disease and limited vaccination intervention. The study sought out to determine the challenges that constrain the effective control of Newcastle among village chickens; to assess the cost-effectiveness of poultry vaccination against this disease and to determine the poultry farmers’ willingness to pay (WTP) for its control through vaccination as well as the underlying factors that influence their willingness to pay. The methodology entailed use of descriptive statistics to establish the challenges whereas the benefit-cost ratio was used to determine the cost-effectiveness of vaccination and the logit model was used to determine the factors influencing poultry keepers’ willingness to pay for vaccination. The major challenges constraining effective Newcastle disease control were high cost of and lack access to vaccines and limited extension services. The costs and benefits pertinent to vaccination were analysed and a Benefit-Cost Ratio of 15:1 was obtained implying that it is cost effective and profitable to vaccinate poultry against Newcastle. Of the 240 poultry keepers in the study, 75% were willing to pay for vaccination and they were willing to pay a minimum of one hundred shillings per chicken which corresponds to the current market price charged for vaccination per bird in the area. Farmers’ income, level of education, membership in a farmer group and total flock size positively and significantly influenced their WTP for vaccination. The female poultry keepers were more likely to pay for vaccination than their male counterparts. Poultry keepers who mainly acquired their stock from the market, those that rear the birds mainly for income as well as those who had lost a large percentage of their flock in a previous outbreak were more likely to pay for vaccination in addition to those who had obtained positive results from previous vaccination. On the other hand, the poultry farmers that had challenges accessing extension services and those staying further away from the trading centres were less likely to pay for vaccination. In order to effectively and sustainably control Newcastle and other poultry diseases, suitable extension programmes need to be developed and extensive disease control and vaccination campaigns should be embarked on with active involvement of the community leaders. Famers are advised to join farmer groups from which they can acquire and share knowledge and work jointly especially in combating epidemics. Government involvement in creating a suitable environment to enhance public-private partnerships in rural areas is of the essence; in addition to improvement of infrastructure in remote places. Since farmers’ level of education significantly affects the decisions they make, it is suggested that community leaders urge them to send their children to school without segregation and the Government should make an effort to improve the quality of education services offered especially in rural areas.