Background: Maxillofacial fractures can lead to massive oronasal bleeding; however, surgical hemostasis and packing procedures can be challenging owing to complex facial anatomy. Only a few studies investigated maxillofacial fractures with massive oronasal hemorrhage. However, thus far, no studies reported a protocolized management approach for maxillofacial trauma from a single center. This study aimed to evaluate the effectiveness of protocolized management for maxillofacial fractures with oronasal bleeding. Methods: Patients were identified from the National Cheng University Hospital trauma registry from 2010 to 2020. We included patients with a face Abbreviated Injury Scale (AIS) score of ≥ 3 and active oronasal bleeding. Patients’ characteristics were compared between the angiography and non-angiography groups and between survivors and nonsurvivors. Results: Forty-nine patients were included. Among them, 34 (69%) underwent angiography, of whom 21 received arterial embolization. Forty-seven patients (96%) successfully achieved hemostasis by adhering to the treatment protocol at our institution. Compared with the non-angiography group, the angiography group had significantly more patients requiring oral intubation (97% vs. 53%, p<0.001), Glasgow Coma Scale <9 (GCS ; 79% vs. 27%, p<0.001), head AIS >3 (65% vs. 13%, p=0.001), higher Injury Severity Score (ISS; 43 [33-50] vs. 22 [18-27], p<0.001), higher incidence of cardiopulmonary resuscitation (CPR; 41% vs. 0%, p=0.002), higher mortality rate (35% vs. 7%, p=0.043), and more units of packed red blood cells transfused within 24 hours (PRBC; 12 [6-20] vs. 2 [0-4], p<0.001). Nonsurvivors had significantly more patients with hypotension (62% vs. 8%; p<0.001), higher need for CPR (85% vs. 8%; p<0.001), head AIS >3 (92% vs. 33%; p<0.001), skull base fracture (100% vs. 64%; p=0.011), GCS <9 (100% vs. 50%; p=0.003), higher ISS (50 [43-57] vs. 29 [19-48]; p<0.001), and more units of PRBC transfused within 24 hours (18 [13-22] vs. 6 [2-12]; p=0.001) compared with survivors. More patients in the nonsurvivor group underwent angiography (92% vs. 61%; p=0.043). Among embolized vessels, the internal maxillary artery (65%) was the most common bleeding site. Hypoxic encephalopathy accounted for 92% of deaths.Conclusions: Maxillofacial fractures with massive oronasal bleeding are rare, but fatal. Securing the airway as well as early hemostasis is the top priority to salvage such patients. Protocol-guided management is effective in optimizing outcomes in patients with maxillofacial bleeding.