The Tokyo Guidelines 2018 (TG18) recommend emergent cholecystectomy (EC) for acute cholecystitis. However, the number of patients on antithrombotic therapy (AT) has increased significantly, and no evidence has yet suggested that EC should be performed for acute cholecystitis in such patients. The aim of this study was to evaluate whether EC is as safe for patients on AT as for patients not on AT. We retrospectively analyzed patients who underwent EC from 2007 to 2018 at a single center. First, patients were divided into two groups according to the use of antithrombotic agents: AT; and no-AT. Second, the AT group was divided into three sub-groups according to the use of single antiplatelet therapy (SAPT), double antiplatelet therapy (DAPT), or anticoagulant with or without antiplatelet therapy (AC ± APT). We then evaluated outcomes of EC among all four groups. The primary outcome was 30- and 90- day mortality rate, and secondary outcomes were morbidity rate and surgical outcomes. A total of 478 patients were enrolled (AT, n = 123, no-AT, n = 355) patients. No differences in morbidity rate (6.5% vs. 3.7%, respectively; P = 0.203), 30-day mortality rate (1.6% vs. 1.4%, respectively; P = 1.0) or 90-day mortality rate (1.6% vs. 1.4%, respectively; P = 1.0) were evident between AT and no-AT groups. Between the no-AT and AC ± APT groups, a significant difference was seen in blood loss (10 mL vs. 114 mL, respectively; P = 0.017). Among the three AT sub-groups and the no-AT group, no differences were evident in morbidity rate (3.7% vs. 8.9% vs. 0% vs. 6.5%, respectively; P = 0.201) or 30-day mortality (1.4% vs. 0% vs. 0% vs. 4.3%, respectively; P = 0.351). No hemorrhagic or thrombotic morbidities were identified after EC in any group. In conclusion, EC for acute cholecystitis is as safe for patients on AT as for patients not on AT.