OBJECTIVES: In this study we explore the methodological challenges presented by retrospective economic analyses of vaccination programs and offer direction for future evaluations in the area. Post-implementation evaluation should be an important part of assessing the success of public health programs; however relatively little attention has been focused on evaluating the value for money achieved by vaccination programs after they have been introduced. METHODS: We conducted a narrative review of the limited existing economic evaluation literature assessing the cost-effectiveness of implemented vaccination programs. We evaluated the alternative approaches to addressing the challenges that these retrospective evaluations present. These challenges were then contrasted and compared with those that prospective economic evaluations face. RESULTS: The key challenges identified for retrospective economic evaluations include the estimation of: disease changes attributable to vaccination efforts, the hypothetical no vaccination comparator scenario and the full benefits likely to be achieved by implemented vaccination programs. We also present other important factors that may need to be considered such as the evolution of prices over time. CONCLUSIONS: Retrospective economic analyses of vaccination programs are likely to become more frequent and influential and it is important that both the benefits and the limitations of these evaluations are recognised and understood. Further work needs to be done to explore how the practical application of alternative approaches may impact on the results of evaluations in different circumstances.