Background: The most prevalent complication following a modified radical mastectomy (MRM) is seroma located under mastectomy flap and/or axilla, with excessive drainage of serous fluid in the drain, long period of the drain inside the wound with risk of infection. Formation of seroma was diagnosed clinically as collection of fluid under the mastectomy flaps and axilla seen as fluctuant, non-tender swelling. Objective: To study the effect of mastectomy flap fixation and axillary space obliteration with separation of both spaces in comparison with classic modified radical mastectomy in diminishing of seroma formation. Patients and methods: This study included 60 female patients over the age of 20 who were undergoing modified radical mastectomy and were randomly divided into two groups of 30 each, Group A (flap fixation, axillary space obliteration, and two space separation) and Group B (non-flap fixation). Mastectomy flaps were sutured to the underlying pectoralis fascia to obliterate the dead space, with axillary space obliteration by suturing flap into serratus anterior muscle and separation of both spaces along the lateral border of the pectoralis major muscle. Results: There was a statistical significant decrease in day of removing the drain, total seroma volume and frequency of postoperative seroma among Group A (with Flap fixation) compared to Group B (without Flap fixation). There was high statistically significant changes in mean total seroma volume between two group, which ranged (250-1100 cc) in group (A) compared with (1500-3500 cc) in group (B). Conclusion: Dead space obliteration following MRM is a simple technique that lowers the incidence of seroma formation, total seroma volume and days of drain removal.