Background: Oxytocin is safe when used correctly. Complications usually follow improper doses or inadequate supervision .Oxytocin administration errors are a significant source of professional liability. Aim: This study aimed at assess the nurses' level of knowledge and practices toward compliance with oxytocin administration protocol during labor. Subjects and Method: A cross sectional descriptive design was adopted. Setting: the study was conducted at Obstetrics and Gynecology department in four hospitals named: Altakhasosy Hospital, Al Azhar Hospital, General Damietta Hospital and Kafr Saad Hospital in Damietta city. Sample: A total of fifty five (55) nurses working in the previous mentioned hospitals were recruited in the study. Tools: Three tools were used for data collection: 1-Structured Self -administered questionnaire, 2- an observational check list and 3- assessment sheet. Results: it Revealed that : about two third of the nurses poor knowledge about use of oxytocin administration protocol , and there was a statistically significant relation between average total knowledge score of studied nurses and their working shift, years of experiencing in nurses. The majority of them had unsatisfactory Practice level, and there was no statistically significant relation between the average total practice score of studied nurses and their demographic characteristics, their work characteristics, only between average total practice score and years of experiencing in midwifery.