BACKGROUND: Despite advancements in surgical techniques and perioperative care for free flap reconstructive surgery, concerns persist regarding the risk of free flap failure, with thrombosis and bleeding being the most common complications that can lead to flap loss. While perioperative anticoagulation management is crucial for optimizing outcomes in free flap reconstructive surgery, standardized protocols remain lacking. This study aims to investigate the role of anticoagulation and perioperative practices in free flap reconstructive surgery and their impact on surgical outcomes. METHODS: This retrospective, single-center study included all adult patients undergoing free flap surgery from 2009 to 2020. Patients were retrospectively divided based on intraoperative (UFH or no UFH) and postoperative anticoagulation management (UFH only, Aspirin and UFH, Aspirin only). The relationship between anticoagulation protocols, PTT values, and flap survival was assessed. RESULTS: A total of 489 free flap surgeries were included. Most flaps were taken from the upper extremity (49.5%), primarily for tumor-related reconstructions (85.7%). Flap loss occurred in 14.5% of cases, with a median time to flap loss of 3 days post-surgery. Intraoperative UFH (20 IU/kg) was administered to 63.6% of patients and significantly predicted flap survival (OR = 0.45, 95% CI [0.24, 0.82]). PTT values on day 1 post-surgery were significantly related to flap survival (P = 0.03), with each unit increase reducing the relative probability of flap loss by 5.2%. There was no significant difference in flap survival between patients treated with heparin alone and those treated with both heparin and aspirin. The small sample size in the aspirin-only group limited the statistical relevance of this subgroup. CONCLUSION: Our findings highlight the importance of intraoperative UFH and PTT-guided postoperative management in improving free flap survival. Standardized anticoagulation protocols are essential for enhancing outcomes in free flap reconstructive surgery.