Purpose: Autologous fat grafting is an invaluable tool which has revolutionized breast reconstruction. However, there has been limited data on the use of pharmacologic agents to mitigate donor site ecchymosis. Antifibrinolytic medications, such as tranexamic acid (TXA) have been demonstrated to safely mitigate ecchymosis, edema, and intraoperative blood loss in plastic surgery procedures. As such, the authors investigate whether topical TXA safely reduces the degree of ecchymosis at liposuction donor sites following autologous fat grafting in the setting of breast reconstruction. Methods: A single-center, single-surgeon retrospective cohort study was performed to analyze all consecutive patients undergoing autologous fat transfer as part of second-stage breast reconstruction between 2016-2019. In all patients, the donor site was infiltrated with Klein’s tumescent solution. Once lipoaspiration was complete, patients in the intervention group received a total of 75mL of topical TXA (3g in NaCl 0.9%) into the harvest donor sites delivered via a spray applicator, whereas the patients in the historical control group did not receive TXA. The primary endpoint was degree of ecchymosis, which was graded on an ordinal assessment tool previously published by Hunstad et al. (1= no bruising” through 10= extremely bruised”). Secondary outcome measures included hematoma, seroma, and thromboembolic events. A double-blinded randomized assessment of postoperative photographs of the donor sites was performed by senior plastic surgery residents and research fellows. Comparative analysis of continuous variables and categorical variables were performed using the Mann-Whitney-Wilcoxon and Fisher’s exact tests, respectively. A value of p<0.05 was considered significant. Results: A total of 120 consecutive autologous fat grafting procedures for breast reconstruction were reviewed. Overall, 60 patients received TXA, whereas 60 patients did not. Patient demographics and comorbidities were similar amongst the groups. There was no difference between groups with regards to donor site locations. There was no difference in volume of tumescent injected amongst the groups. The median tumescent volume infiltrated in the TXA group was 1600mL (range: 1200-2400mL), and 1750mL (range: 800-2500mL) in the non-intervention group (p=0.86). Median volume of lipoaspirate amongst the TXA and control groups was similar: 317.5mL (range: 45-750) vs. 267.5mL (range: 55-905), p=0.44. A total of 10 blinded evaluators completed the assessment (7 senior plastic surgery residents and 3 research fellows). Average time to postoperative photograph for the TXA group was 14±13 days vs. 10.3±6.2 days for the non-intervention group (p=0.11). The median bruising score of patients who received TXA was significantly lower than the patients who did not (1.6/10 vs. 2.3/10, p=0.01). Postoperative complications, including hematoma, seroma, and thromboembolic events were similar amongst the groups. Adverse effects of TXA were not observed. Conclusion: As the role of TXA in plastic surgery increases, there remains a recognizable gap in the literature with regards to its use in autologous fat transfer procedures. Although, further prospective randomized studies are warranted, the authors demonstrate that patients who received topical TXA into the liposuction donor sites were found to have less donor site ecchymosis compared to patients who did not receive TXA.