The optimal perioperative antithrombosis management for carotid artery stenting (CAS) and coronary artery bypass grafting (CABG) hybrid surgeries remains unclear; however, a more aggressive antithrombotic therapy might be required after a hybrid CAS+CABG duo stent-related intimal injury or the use of protamine-neutralizing heparin. This study evaluated the safety and efficacy of tirofiban as a bridging therapy after a hybrid CAS+CABG surgery. Between June 2018 and February 2022, a total of 45 patients undergoing a hybrid CAS+off-pump CABG surgery were divided into either the control group (standard dual antiplatelet therapy postsurgery, n=27) or the tirofiban group (tirofiban bridging+dual antiplatelet therapy, n=18). The 30-day outcome was compared between the 2 groups, and the primary end points included stroke, postoperative myocardial infarction, and death. Two patients (7.41%) from the control group experienced a stroke. There was a trend toward a lower rate of composite end points, including stroke, postoperative myocardial infarction, and death, within the tirofiban group that did not reach statistical significance (0% vs 11.1%; P=0.264). The need for a transfusion was similar between the 2 groups (33.33% vs 29.63%; P=0.793). There were no major bleeding events in the 2 groups. Tirofiban bridging therapy was safe, with a trend toward reducing the risk of ischemic events after a hybrid CAS+off-pump CABG surgery. Tirofiban might be a feasible periprocedural bridging protocol in high-risk patients.