Background: Breast cancer ranks as the second most common cancer worldwide and by far the most prevalent cancer among women. A common side effect following a modified radical mastectomy or wide local excision with lymph node dissection is the buildup of fluid and Seroma. Methods: This study included 150 female patients who underwent mastectomy due to cancer. It was a prospective, randomized, and controlled study where they were divided into three groups at random: group I consisted of fifty women who had fibrin glue sprayed on their axilla and mastectomy bed and had suction drains placed. In group II, fifty women had flap fixation using sutures with low vacuum drainage. In group III, fifty women had traditional closure with low vacuum drainage. Results: With a mean of 489±188.7 ml , patients with quilted flaps in our study showed the lowest seroma volumes with a statistical significance (p value < 0.001). Quilting sutures reduced the frequency of aspiration, with a lowest median of 2.0 (0-3) (P = 0.046). It also had the lowest number of drain reinsertion, with a statistically significant difference (P = 0.029). The mean drainage periods for Group I and Group II were found to be 9 and 5 days, respectively (P = 0.03). Conclusion: Our research led us to conclude that quilting flaps following mastectomy is a useful strategy for significantly cutting down on the amount of time and volume of wound drainage and reducing postoperative seroma.