Order picking is the process of retrieving products from storage in response to a specific customer order. Although this process’ design has significant impact on warehouse global performance, a practical-oriented design procedure is still lacking in literature. This paper presents a novel order picking system design methodology based on Design for Six Sigma approach, that aims to assist designers making decisions by suggesting the most effective operational and organizational policies and the equipment needed in order to fulfill customer’s orders. A case research in a home appliances manufacturer is presented in order to demonstrate the effectiveness of this approach.