Background: Seroma is a strange gathering of serous fluid within the dead space of post-mastectomy skin flaps and axilla, or after breast-conserving surgery [BCS]. Seroma is one of the most commonly reported early post-operative problems following breast cancer [BC] surgery. According to several studies, after a modified radical mastectomy [MRM] or axillary lymph node dissection [ALND], the incidence ranges from 10% to 85%.  
The Aim of The Work: The current study aimed to investigate the efficiency of two methods in preventing seroma development after BC surgery.
Patients and Methods: From December 2018 to January 2022, this prospective comparative study was conducted in the Department of General Surgery, Faculty of Medicine, Al-Azhar University, Assiut, Egypt. Throughout the study period, cases scheduled for MRM had randomly assigned to one of two groups: mastectomy flap fixation [15 cases] or ipsilateral shoulder immobilization [15 cases].
Results: Throughout the study period, 30 patients were recruited, 15 patients in group A [flap fixation] and 15 patients in group B [shoulder immobilization]. The proportion of patients who developed seroma requiring aspiration was 40% [n=6] in shoulder immobilization group and no reported cases [n=0] in Flap fixation group [p= 0.006]. In addition, the total amount of drained fluid was 803.3 ml in flap fixation group and 950 mL in shoulder immobilization [p= 0.003]. Regarding Shoulder stiffness, 60% [n=9] in shoulder immobilization group and no reported cases [n=0] in Flap fixation group [p= 0.006]. Flap fixation was determined to be the most effective technique for preventing seroma formation, with a low rate of established seroma and associated problems. Ipsilateral shoulder immobilization, on the other hand, has a limited function in the prevention of established seroma following MRM. 
Conclusion: The mastectomy flap fixation operation is an effective maneuver to decrease seroma and reducing the volume and duration of drained fluid.