Background: Lymphedema is one of the riskiest and most prevalent complications post-mastectomy that interfere upper limb function which negatively affect their quality of life. Aim: Evaluate the effect of compression garment (CG) along with shoulder exercise on reducing lymphedema and enhancing upper limb function among post mastectomy women. Method: Research design: A quasi experimental research design with a control group was used. Subjects: A total of 120 women with breast cancer were evenly and randomly allocated to the intervention and control group. Women in the interventional arm were directed to apply compression garmet during exercise for six months post operatively. The control group received routine hospital postoperative care. Tools: 1. Demographic and health relevant form, 2. Shoulder Pain and Disability index questionnaire, 3. Shoulder flexibility and grip strength, 4. lymphedema and arm circumference scale. Results: At a 6-month interval, the occurrence of lymphedema was markedly lower in the intervention group (p = 0.000) compared to their control and there were statistically significant differences between study groups as regard shoulder pain and upper limb function (p=0.000). Conclusion: Post mastectomy exercises combined with compression garment is very effective in preventing lymphedema and improving upper limb function in post-mastectomized women. Recommendations and Relevance to clinical practice: Low-intensity exercises and compression garment is a safe, effective, non-invasive method that should be incorporated into the management of post-mastectomy patients to prevent lymphedema and enhance upper limb function.