Background: Emergency cholecystectomy is the standard treatment for acute cholecystitis, but managing patients on antithrombotic therapy poses significant challenges due to ‘an increased risk of bleeding’. This study evaluates the impact of antithrombotic therapy on surgical outcomes, including bleeding complications, in patients undergoing emergency cholecystectomy. Methods: ‘A cross-sectional observational study was conducted at a Maqsood Medical Complex and General Hospital Peshawar from January 2023 to January 2024’. One hundred-one patients diagnosed with acute cholecystitis were included and divided into the antithrombotic (n=51) and non-antithrombotic (n=50) groups. Data on demographics, laboratory parameters, surgical details, and postoperative outcomes were collected and analyzed using appropriate statistical methods. Results: Patients in the antithrombotic group exhibited significantly higher intraoperative blood loss (310 mL vs. 140 mL, P=0.001) and postoperative bleeding rates (19.6% vs. 6%, P=0.03) compared to the non-antithrombotic group. Blood transfusion requirements were more significant in the antithrombotic group (23.5% vs. 8%, P=0.02), and hospital stays were more extended (7 days vs. 4 days, P=0.001). However, mortality rates were comparable between the groups (3.9% vs. 2%, P=0.60). Conclusion: Antithrombotic therapy is associated with increased bleeding complications, and more extended hospital stays in emergency cholecystectomy for acute cholecystitis. Despite these challenges, mortality rates remained unaffected, highlighting the importance of careful perioperative management to mitigate risks. Further research is needed to develop standardised protocols for managing this high-risk population.