Background: One of the method to improve hospital quality services is by improving performance in the application of patient safety. Nurses are health workers who held key of success on patient safety. Effective leadership from the head nurses, workload and work motivation of nurses are considered to be an important factor in improving the performance of patient safety by nurses. Method: Type of study was quantitative research with cross-sectional design. Knowing effective leadership, workload and motivation of 76 nurses for performing patient safety at ward rooms of PKU Muhammadiyah Bantul Hospital during July to August 2018. Data analysis using multiple logistic regression. Results: This study showed the significant result (p value < 0,05) with p value of effective leadership 0,033, workload 0,027 , and motivation 0,017. Conclusions: Effective leadership has an influence on nurses performance in the application of patient safety. Workload has an influence on nurses performance in the application of patient safety. Motivation is the most influential on nurses performance in the application of patient safety. Keyword: Effective leadership, workload, motivation, performance, patient safety