Background: Patient safety is the core of the quality of health services in hospitals. To achieve this requires a strong commitment from each individual and team. Various ways are done to improve the quality of service in hospitals, one of which is by increasing the performance of nurses in the application of patient safety. As one of the components of human resources who work directly on the front lines, nurses have more time to deal with patients. Methods: This study uses quantitative research methods to test and prove the hypotheses that have been made. The number of samples is 76 respondents using a Likert scale questionnaire research instrument which will be analyzed using Structural Equation Modelling-Partial Least Square (SEM-PLS) with SmartPLS 3.2.9. Results: Motivation and workload can play a good role as intervening variables. The direct influence of effective leadership, workload, and work motivation showed significant and positive results on the performance of nurses in the application of patient safety in the inpatient room of AM Parikesit Hospital, Tenggarong. Conclusion: There is a positive and significant influence on effective leadership, workload, work motivation on nurse performance, as well as motivation and workload that can be an intervening variable in this study.