Background: Acute organophosphate poisoning is a major health problem presents worldwide and is responsible for many mortalities especially in developing countries. Early identification and effective management in the initial stages increase rate of survival among these patients. Nurses' role remains long standing determinates of quality care rendered for patients, many factors affecting nurses' role include physical, psychological, professional, patient related factors and work-related factors. so, nurses' play a core role in the management of acute organophosphate poisoning through closely monitoring of patients and providing quality nursing care. Aim of the study was to determine factors affecting nurses' role regarding care of patients with acute organophosphate poisoning. Research design: A descriptive design was used; research design should be carefully developed to ensure that the results are valid and reliable. Subjects and Methods: Research design: A descriptive research design was carried out in this study Setting: The present study was conducted in emergency department and poisoning unit at Zagazig university hospitals Subjects: A convenience sample of all available nurses (70). Tool of data collection: Two tools were used for collecting data: A structured interview questionnaire about demographic characteristics of the studied nurses, nurses` knowledge, and factor which affect nurses' role. Observational checklist to assess nurses' practices. Results: More than three quarters (75.7%) of studied nurses had unsatisfactory total knowledge, more than two thirds (68.6. %) of studied nurses had unsatisfactory total practice regarding care of patients with acute organophosphate poisoning and 67.1%, 58.6% & 77.1% of factors related to nurse, factors related to patient, and factors related to work respectively affected nurses' role regarding care of patients with acute organophosphate poisoning. Conclusion: There was a positive significant correlation between total knowledge, total practice, and factors affecting nurses' role. Recommendation: Training programs are recommended to improve nurses' knowledge and practice regarding care of patients with acute organophosphate poisoning. Factors affecting nurses' role should be evaluated by the nursing management and hospital administration to avoid or correct such factors.