Breast cancer is the most common cancer and main cause of cancer death in women and nurses can provide holistic care through application of nursing models. Aim: To evaluate the effect of application Roy's adaptation model on women's satisfaction and quality of life after mastectomy. Design: A quasi- experimental design was utilized. Setting: The study was conducted on the Oncology Department at Benha University Hospital and Health Insurance Hospital at Benha City, Egypt. Sampling: A purposive sample included 100 women involving two groups (study and control). Tools: Three tools were utilized to collect data and included a structured interviewing questionnaire, Breast-QTM-Mastectomy Module and Roy's Adaptation Model. Results: There was a highly significant difference between study and control groups regarding total knowledge, total satisfaction and total quality of life after two weeks of program implementation and after three months of follow up (P ≤ 0.001). Also, there were high significant differences in all domains of maladaptive behaviors after the program implementation in the study group (P ≤ 0.001), while it was not significantly different in the control group. Conclusion: The application of Roy's adaptation model was effective on improving post mastectomy women's knowledge, satisfaction and quality of life also, promoted women's adaptation to the disease and treatment regimen. Recommendation: An educational program should be provided to all nurses on the oncology departments to promote their knowledge to educate women about disease and management.