Introduction: After a mastectomy, lymphedema is a possible side effect. The improvement of the lymphatic system is the most important aspect of Lymphedema treatment. Lymphedema can be treated effectively with manual lymphatic drainage (MLD). Aims: The core of the current study is to draw a comparison that highlights the effects of the Vodder MLD and the Casley-Smith MLD on post-mastectomy lymphedema. Methods: For the study, thirty female patients with post-mastectomy lymphedema were divided into two equal groups at random. Vodder MLD Technique, Pneumatic Compression Pump, and Bandage were given to Group (A). Casley-Smith MLD Technique, Pneumatic Compression Pump, and Bandage were given to Group (B). Each participant's intervention lasted eight weeks, with three sessions every week. Results: The results showed that employing two distinct treatment procedures improved both groups significantly (P < 0.001). There is not a clear disparity between the two study categories (P > 0.05). Conclusion: The MLD techniques of both Vodder and Casley-Smith are helpful in providing a treatment for the lymphedema post mastectomy. There is no difference between the two techniques. Subsequently, any MLD technique is highly recommended to produce better results in lymphedema therapy after mastectomy.