Background: Cholecystectomy surgery, is a surgical procedure involving the removal of the gallbladder to relieve symptoms such as abdominal pain and prevent serious complications associated with gallbladder disease. Postoperative nursing instructions for patients undergoing cholecystectomy are crucial for optimizing recovery, preventing complications, and enhancing quality of life. The aim of the study: was to evaluate the effect of post operative nursing instructions for cholecystectomy patients on their knowledge and life style change. Study design: Quasi experimental research design (pre/post) was used to conduct the aim of this study. Setting: The study was conducted in Surgical Department and Outpatient Clinics at Benha University Hospital, Qualyubia Governorate, Egypt. Subjects: A purposive sample of (58) adult patients undergoing cholecystectomy surgery. Tools: Two tools were used; tool (I): A structured interviewing questionnaire, it involved the patients' personal data, medical history and patients' knowledge assessment. Tool (II): Health promoting lifestyle profile questionnaire, it involved six domains; nutrition, physical activity, health responsibility, spiritual growth, stress management and interpersonal relations. Results: The results of this study revealed that, there was highly statistically significant difference in total knowledge levels between pre and post nursing instructions implementation periods. Where, (72.4% & 60.3%, respectively) of studied patients had satisfactory level of total knowledge about cholecystectomy during immediate, and post 2 months periods of nursing instructions compared to 15.5% of patients pre nursing instructions period and a highly significant statistical difference in health-promoting lifestyle following the nursing instructions with p value =