Background: In the majority of nations worldwide, postpartum hemorrhage (PPH) remains the primary cause of mother morbidity and death. Aim: The aim of the study was to evaluate effect of who guideline on nurses' knowledge regarding prevention and management of postpartum hemorrhage. Subjects and method: A quasi-experimental (one group pre- posttest) design was employed in this investigation. The study was conducted at Women's Health House Hospital (previously named Specialized Women and Obstetrics Hospital (affiliated to Egypt health care authority hospitals in Port Said). Sample: All 150 nurses employed at the time of the study at the Women's Health House Hospital were included in a convenience sample for the purpose of the study. Data collection tool: A structured interviewing form was used to collect relevant data. It includes personal characteristics about the study subjects such as: age, marital status, educational level, years of experience, residence and previous training courses about PPH, and nurse's knowledge regarding prevention and management of postpartum hemorrhage. Results: The majority of the studied nurses had satisfactory level of total knowledge regarding nursing interventions for prevention and management of PPH post applying WHO guidelines (78.0% & 94.0%, respectively) compared to the minority of them had unsatisfactory level of knowledge pre- applying WHO guidelines (4.0%6.0%, respectively). Conclusion: Following the implementation of the recommendations issued by the WHO for the prevention and management of postpartum hemorrhage, the investigated nurses' knowledge significantly improved. Recommendations: It is recommended that intern nurses be provided with periodic health education programs in order to improve their knowledge and abilities in order to provide advanced nursing care with respect to the prevention and treatment of primary postpartum hemorrhage.