Objective: To compare the effect of flap fixation and non-flap fixation for preventing seroma formation depending upon stage of surgery in patients undergoing mastectomy at RMU Allied Hospitals following mastectomy in our local population. Study Design: Randomized Controlled Trial. Setting: Surgical Units of Holy Family Hospital, Benazir Bhutto Hospital, DHQ Hospital (RMU & Allied Hospital). Period: October 2020 to April 2021. Material & Methods: Sample size of 114 cases was included in the study. It was Non probability, consecutive sampling technique. Patients were equally randomized to flap-fixation (Group A) and non-flap fixation (Group B). Patients of both groups were followed up to 48 hours postoperatively for seroma formation. Results were analysed using SPSS software and compared by applying chi-square test and p-value ≤0.05 considered significant. Results: Statistically significant difference (p-value ≤0.05) for seroma formation was noted only in disease stage IIIA. In group A (Flap Fixation), seroma formation was noted in 22.8% (n=13) patients, while in group B (Non-Flap Fixation) it was noted in 45.6% (n=26) patients only. Conclusion: The patients with stage IIIA undergoing mastectomy are significantly (p-value ≤0.05) associated with seroma formation. Whereas, flap fixation is more useful technique for minimizing seroma formation.