The subject of patient safety culture has attracted international interest. However, implementing these patient safety policies and practices is not easy, as significant challenges remain. This study analyzes the influence of clinical leadership effectiveness on patient safety culture by distributing questionnaires to 237 nurses in Hospital “X” in West Nusa Tenggara. Structural Equation Modeling (SEM) based on Partial Least Square (PLS) was used for data analysis and knowledge management was placed as a mediating variable in this study. It was found that the effectiveness of clinical leadership has a significant effect on patient safety culture. Thus, this study opens the scope of clinical leadership research in hospitals by exploring the effectiveness of leadership on patient safety culture. The role of clinical leaders in creating a patient safety culture with the mediation of knowledge management was also examined.