Background: Program budgeting and marginal analysis (PBMA) is a framework for setting priorities in health care, used internationally over the last 25 years in Britain, Australia and New Zealand. However, the framework has undergone limited evaluation, and insight into how such evaluation should even take place is not found in the literature. Methods: Seven PBMA case studies were conducted in three Canadian health regions to examine the feasibility of applying the PBMA framework. Structured follow-up surveys with the users of the framework were carried out following the priority setting exercises. Results: The PBMA framework was feasibly implemented in three regionalized contexts and was generally viewed favorably by managers and clinicians who participated in the case studies. Numerous methodological lessons were learned and it was found that successful implementation hinges on organizational context. An empirically derived model describing PBMA is outlined and put forth as an evaluation framework for future exercises. Conclusions: Comparisons to the health care management literature indicate that the derived PBMA model is a novel addition to this broader literature. Overall, managers in health organizations internationally would be well-served to consider PBMA to aid regional decision-making processes, but should do so with explicit consideration of the context in which such activity is to occur.