In the last decade, the rapid economic development in the Middle East has encouraged organisations to implement modem quality management and strategic initiatives such as Six Sigma to ensure continuous improvement and achieved excellence. Six Sigma is a comprehensive business strategic quality programme and a systematic process improvement methodology for achieving, sustaining and maximising business success. The proper implementation of Six Sigma leads to breakthrough in profitability through ensuring quantum gains in product/service quality, customer satisfaction and productivity. This research presents an empirical exploratory and comparative study that aims and attempts to bridge the gap in the existing literature of Six Sigma by investigating the current implementation status of Six Sigma in organisations of three Middle East countries (namely, Saudi Arabia, Egypt and United Arab Emirates (UAE)). The reasons/benefits that encourage Middle East organisations to implement Six Sigma projects, the challenges commonly faced during implementation, the critical success factors (CSFs) for effective implementation and the organisations’ satisfaction with the implementation are investigated. The key issues of Six Sigma implementation and their criticality relating to the experience of the implementing process of Six Sigma projects are explored through an extensive review of the relevant literature. The data were collected from a combination of quantitative (232 questionnaires) and qualitative (74 semi-structured interviews) methodologies. The research covered 44 organisations from manufacturing and services sectors and large, small, and medium enterprises (SME) sizes, which have implemented or were implementing Six Sigma projects in the selected countries at the time of study. The study findings identified 15 significant reasons/benefits which encourages Middle East organisations to implement Six Sigma projects, 13 major challenges commonly faced during implementation, 19 CSFs for effective implementation and level of the organisations’ satisfaction with the implementation. Based on the research findings, a generic model for successful and effective implementation of Six Sigma in Middle East organisations is developed and proposed. The research concludes that Six Sigma implementation in Middle East organisations still in early stage, most organisations have outstanding opportunities to implement the Six Sigma project successfully and effectively with tangible and intangible benefits. In addition, all the responding organisations, which are actively implementing Six Sigma programme, regardless of their countries, sectors and sizes are highly satisfied with the implementation results. However, the research output highlights that an improvement culture must be developed and promoted throughout the organisation to ensure long-term benefit and sustainable success. Furthermore, the research makes recommendations on development of an implementation strategy in Middle East organisations. Finally, a number of suggestions are made for future research.