Background: Proximal humerus fractures (PHF) are very common and a serious health problem. They are the seventh most frequent fractures in adults. Simulation-based training serves as a link between classroom learning and clinical practice. It aids nursing competency before working with patients in a real-life environment, hence improving the quality of care and ensuring patients' safety. This study aimed to evaluate the effect of simulation-based training on nurses' performance regarding care of patients undergoing humeral fracture surgery. Method: A quasi-experimental design (one group pre/ post-test design) was used. Setting: The study was conducted in orthopedic wards at Mansoura University Hospital. Subjects: All nurses (50) who were working in the previously mentioned setting during the study period regardless of their age, education, or years of experience. Tools for data collection: Tool (1) Humeral fracture surgery questionnaire sheet included Part 1: Demographic characteristics of nurses &Part (2): The nurses' knowledge of humeral fracture surgery, and Tool (2) Humeral fracture surgery's observational checklist were used to collect data. Results: There was a highly statistically significant difference in the knowledge and practice of the nurses under study. Before the introduction of simulation-based training, the study's findings showed that over two-thirds of the nurses under investigation had a poor level of knowledge regarding care of patients undergoing humeral fracture surgery, and over half of them had incompetent level of practice. After putting simulation-based training into practice, the great majority of the nurses under study had a good level of knowledge, and a competent level of practice. There was a highly statistically significant difference and improvement in nurses' performance after simulation-based training compared pre- training. Conclusion: The present study concluded that simulation-based training had a positive effect on improving nurses' performance regarding care of patients undergoing humeral fracture surgery. Recommendations: The study recommended that simulation-based training should be integrated as an effective method in nurses' training regarding care of patients undergoing humeral fracture surgery.