Background: The third stage of labor is a critical period, associated with serious complications mainly postpartum hemorrhage. So, the aim of this study was to determine the effect of high fidelity simulation on intern students' competency regarding clinical guidelines for active management of the third stage of labor. Subjects and Method: A quasi experimental study design was utilized to conduct this study on 50 intern students who were training at labor unit, obstetric department, Tanta University Hospitals. The study was carried out at Objective Structure Clinical Examination (OSCE) skill lab, Faculty of Nursing, Tanta University, Egypt. Three tools were used: Tool (I): A structured interview schedule included three parts, Tool (II): Intern students' practice observational checklist& Tool (III): Modified Self-Confidence Measurement Scale. Results: The results of the present study showed statistically significant improvements in intern students' knowledge, practice and self-confidence regarding clinical guidelines for active management of the third stage of labor immediately and one month post simulation training program (P <0.001). Conclusion: Based on the findings of the present study, it can be concluded that high fidelity simulation training significantly enhanced the intern students' competency regarding clinical guidelines for active management of the third stage of labor. Therefore, the study recommended that providing pre-service and in-service training programs using high fidelity simulation especially for newly appointed intern nurses is crucial to improve their clinical competency.