Six Sigma is used heavily in various industrial sectors, yet no noticeable applications are seen in healthcare logistics. This paper reveals the special case of healthcare logistics where cost reduction is not the only factor considered in project selection; performance and criticality of each item in the logistics system are of high importance as well. This paper provides a proposed framework to apply Six Sigma in the area of healthcare logistics. It also presents a case study implementing the proposed framework at a Jordanian hospital. In the case study, the paper reveals how the modifications of the define phase to take into consideration the criticality, cost, and performance of items make typical Six Sigma methodology very beneficial for healthcare logistics. In addition, it shows how the Six Sigma project selection can be done to deal effectively with healthcare logistics issues. This paper paves the road for research to elaborate on ways to use Six Sigma in the area of improving healthcare logistics.