To improve their services and maintain patients’ satisfaction, healthcare organisations have adopted and applied different quality tools and models in recent times, with some even developing their own quality-based initiatives. For example, the approach of Lean Six Sigma (L6σ) has recently been gradually and slowly implemented in healthcare institutions. However, the nature and complexity of healthcare environment which directly impact on humans require leaders to carefully apply appropriate Quality Management (QM) systems suitable for this critical environment. The aim of this research project is to develop a Knowledge Based System (KBS) to assist healthcare managers and practitioners during decision-making process in the context of achieving excellent benchmark and action plans prioritisation. The system will be built based on a conceptual framework for Quality Management in Healthcare Environment (QMHE) which will be modified into a model. The KBS will be developed from this model with the integration of Gauging Absence of Pre-requisite (GAP) method for benchmarking and Analytical Hierarchy Process (AHP) method for prioritisation. The contribution of this research is the use of KBS with GAP and AHP to develop an integrated Knowledge-Based Lean Six Sigma (KB-L6σ) in QMHE. This will accomplish the necessities of investigating quality problems and recommend suitable solutions according to international best practices. It will use a systematic approach that can be applied multiple times, follow defined steps to secure consistency in the approach and integrate different healthcare management levels to maintain strategic decision-making alignment. It consists of 964 KB rules that have been produced via a knowledge acquisition process from the literature and interviewing experts in the field of QM and L6σ in healthcare environment. Feedback from conferences and system testing were used for the verification of the model, whilst validation was carried out through three case studies implementation at three tertiary hospitals in Oman. The analysis of using the KB system in these hospitals has shown clearly that the developed system is a consistent and reliable methodology for assisting decision-makers in designing, planning, and implementing L6σ for QMHE.