In 2015, the OIE and FAO launched a global eradication programme for Peste des Petits Ruminants (PPR). Vaccination is a major component of this strategy yet the costs of implementing a campaign are unknown or based on assumptions without field-based verification necessary for effective economic planning. This study used experiences of attending four PPR vaccination campaigns in Ethiopia to estimate various cost components in pastoral and mixed-crop livestock systems. These components included: cost of vaccine; vaccine transport from the producer to the local storage facility; storage of vaccine at the local facility; delivery and administration of vaccine in the field; opportunity cost of farmer’s time to attend the vaccination; co-ordination of vaccination campaign; publicity and mobilisation costs; vaccine wastage from missed shots and vaccine discard. The overall cost of vaccination was approximately 6 Ethiopian birr (ETB) or US$0.2 per animal in the mixed-crop livestock system compared to approximately 3ETB or US$0.1 in pastoral areas. The relative importance of cost components varied in the two systems with farmer time being the largest contributor in the mixed-crop livestock system while field delivery was the main cost in pastoral areas. Notable vaccine wastage was observed particularly through missed shots that were typically between 0 and 10% but as high as 33%. At the national level, the output of the stochastic model showed the cost of vaccination to be highly variable particularly in the mixed-crop livestock system. These results highlight the importance of doing economic assessments of vaccination campaigns and issues that may be compromising efficiency of delivery and vaccine coverage. It is recommended that the framework be used for further economic evaluations of vaccination for PPR and other livestock diseases particularly when limited public or donor funds are being used, and that the approach be expanded to other countries and regions.