Background: Lymphedema is the build-up of lymph fluid in the tissues just under the skin. Lymphedema following mastectomy as a treatment for breast cancer is a major concern for most women who experience it. Physical activities are very helpful for lymphedema control. Aim: To evaluate the effect of prophylactic physical activities on reducing lymphedema among women post-mastectomy. Subjects & Method: Design: A Quasiexperimental design was utilized. Setting: This study was carried out in Minia oncology center-outpatient and inpatient surgical department. Affiliated by Secretariat of Specialized Medical Centres, at Minia Governorate, Egypt. Subjects: Included a total of 200 women have had a mastectomy. Tools: Five tools were used. 1) structured questionnaire; 2) scale for pitting edema measurement; 3) scale for lymphedema stage assessment; 4) international physical activity Questionnaire; 5) observational checklist for Physical Activities performance. Results: The mean age of the sample was 58.9 years old and 52.5% of them were elderly women. During the first assessment, more than eighty percent of the sample complained from a stage1 lymphedema. However, there was a significant reduction in this percentage among the study group during post-test. Likewise, there was a statistically significant difference between the groups regarding the lymphedema time and stage of development during the first assessment, after 6 weeks and 16 weeks (P<0.001*). Moreover, 49.0% of the study group compared to 29.0% of the control group had a moderate level of physical activity during the post-test. This indicated an increase in the level of a total pattern of physical activity between the two groups during the post-test. Conclusion: Prophylactic physical activities can reduce lymphedema associated symptoms. Also, the study group had a better level of physical activities than the control group. Recommendations: Early detection and nursing interventions have been gradually advocated to prevent lymphedema progression. So, the prophylactic physical activities are essential measures post-mastectomy to reduce lymphedema.