The Lean Six Sigma is one the most effective methods of total quality management to continuously improve the quality performance of the organizations. This approach continuously improves the performance of healthcare organizations by reducing the number of errors towards patient safety. The present study investigates the influence of Lean Six Sigma on patient safety towards the quality improvement of Malaysian hospitals. This study applied a quantitative research approach and a stratified random sampling method to analyze 16 public and private hospitals. It was used a self-administered survey questionnaire to collect data from 364 respondents. This study developed a research model with four hypotheses. All hypotheses were tested using the Partial Least Squares – Structural Equation Modeling (PLS-SEM) method. The research findings indicate that Lean Six Sigma has a strong positive and significant effect on patient safety and quality improvement of the hospitals. The results of the study also indicate that the Lean Six Sigma method indirectly influences the quality improvement of the hospitals through the mediating effect of patient safety. The present research findings provide a guideline for the practitioners of the healthcare organizations to implement the Lean Six Sigma approach to ensure greater patient safety towards the continuous quality improvement of the healthcare services.