The knowledge that they have breast cancer and the loss of their physical attractiveness are two major concerns that women who have had a mastectomy for the disease contend with. Wearing an external breast prosthesis after a mastectomy is chosen to lessen psychological stress and replace the weight of the missing breast. Aim: To evaluate the effectiveness of educational guidelines on post-mastectomy women's knowledge, practices, and psychological stress regarding external breast prostheses. Subjects and method: Design: The goal of this study was accomplished by using a quasi-experimental research approach. Setting: The study was conducted in Minia Oncology Center's Inpatient and Outpatient clinics / Mania Governate/ Egypt. Subjects: A purposive sample of 50 post-mastectomy women were recruited in this study. Four tools were used: Tool (I) structured interviewing questionnaire, which included two parts: (a) demographic characteristics of post-mastectomy women; (b) post-mastectomy women's medical data, Tool (II) post-mastectomy women's knowledge regarding external breast prosthesis, Tool (III) post-mastectomy women ' practice regarding external breast prosthesis (pre/post), and Tool (IV) Depression, Anxiety, and Stress Scale (DASS-21) (pre/post). Results: The study's findings demonstrated that there were statistically significant differences and improvements in knowledge, practice, and psychological stress post-educational guidelines than pre-educational guidelines among post-astectomy women. Conclusion: The results of the study concluded that the educational guidelines were effective in improving post-mastectomy women's knowledge, practice, and psychological stress regarding external breast prostheses. Recommendations: It recommended raising awareness of post-mastectomy women about external breast prostheses during follow-up by incorporating this information in their care and follow-up.