Background: Cholecystectomy is the surgical removal of the gallbladder and is one of the most common abdominal surgical procedures today. Aim of the study: was to assess nurses' knowledge and practice regarding care for patients undergoing cholecystectomy. Design: A descriptive exploratory design was utilized. Setting: The study was conducted at three surgical departments at Zagazig University Hospitals, hepatic surgery and endoscopy department, general surgery department and vascular surgery department. Subjects: The study was conducted on convenience sample of available nurses working in surgical departments and caring for patients undergoing cholecystectomy. Tools of data collection: Two tools were used; an interviewing questionnaire and an observational checklist. Results: More than half (52%) of studied nurses aged less than 30 years old, 92% of the studied nurses were females and married, 40% of the studied nurses had diploma degree and 44% of the studied nurses worked in general surgery department, 52% of studied nurses had less than ten years of experience in surgical departments and 100% of studied nurses didn't receive any training program about cholecystectomy. 82% of the studied nurses had unsatisfactory level of knowledge, while about 92% of the studied nurses had unsatisfactory level of practices. There was a highly statistical significant relation between nurses' knowledge regarding care for patients undergoing cholecystectomy and their education level. There was a statistical significant relation between nurses' practice and their age and years of experience. There was a statistically positive correlation between nurses' knowledge score, and their practice score. Conclusion: The researcher can concluded that the studied nurses had unsatisfactory knowledge and practice. Recommendations: Continuous in-service training programs are recommended to improve and maintain nurses’ performance regarding care for patients undergoing cholecystectomy.