Purpose <p>To investigate the impact of antithrombotic therapy on the clinical outcomes of emergency laparoscopic cholecystectomy for acute cholecystitis. </p> Methods <p>A single-center retrospective surgical database included 550 patients who underwent emergency cholecystectomy between 2005 and 2025, and the current study population included 329 patients who underwent emergency laparoscopic cholecystectomy, excluding open cholecystectomy and chronic cholecystitis. Patients were divided into two groups: patients receiving antithrombotic therapy (ATT, n = 143) and those not receiving antithrombotic therapy (non-ATT, n = 186). The ATT group was divided into aspirin monotherapy (aspirin, n = 62) and multiple antithrombotic therapy (mATT, n = 21) groups. Outcome variables were compared between the groups, and risk factors for intraoperative blood loss were assessed using logistic multivariate analysis.</p> Results <p>The overall rate of severe postoperative complications was 2.7% and the surgical mortality was zero in the entire cohort. Intraoperative blood loss was significantly larger in the ATT group. A multivariate analysis showed that dialysis (odds ratio: 5.210, P = 0.019) and severe acute cholecystitis (odds ratio: 2.630, P &lt; 0.001) were significant risk factors for increased intraoperative blood loss. There were no significant differences in the perioperative outcomes between the aspirin and mATT groups.</p> Conclusion <p>Although dialysis and severe acute cholecystitis contribute to increased intraoperative blood loss, emergency laparoscopic cholecystectomy may be performed safely, even in patients receiving multiple antithrombotic therapies.</p>