Background Seroma formation is considered the most frequent postoperative complication after breast cancer surgery. Serous fluid is collected just under the skin flaps or in the axillary pace immediately following mastectomy preventing adherence of the flaps to the underlying fascia and muscles leading to delay wound healing, infected wound due to repeated aspiration, wound dehiscence, prolonged hospital stay, delay of adjuvant treatment, and finally generating additional costs. Patients and methods A randomized, controlled study was carried out among 138 female patients, who were candidates for mastectomy and axillary clearance. A control group without quilting (69 patients) had a traditional wound closure and the intervention (quilted) group (69 patients) had a sutured flap fixation. Results There were significant differences regarding seroma formation between both groups since it was detected in 22 (31.9%) of the 69 in the suture group and in 39 (56.5%) of 69 in the control group (P<0.004). There were significant differences between means of the number of seroma aspirations among patients with seroma (n=61) by study groups being significantly reduced in in the quilting group (4.3%) versus (18.8%) in the nonquilting group in comparison to the nonquilting group with P value less than 0.008. The range of operative time was 146 (80–160) in the quilting group and 100 (70–135) in the control group. Conclusion Quilting sutures postmastectomy is the most advised technique to minimize seroma formation and its complications. Hence, we recommend quilting of flaps as a routine step at the end of any mastectomy. Keywords: breast cancer, flap fixation, mastectomy, quilting, seroma