Background: Massive hemorrhages occur in 6%-10% of patients with advanced cancer. Acute carotid blowout syndrome is the most severe massive hemorrhagic complication in head and neck cancer patients. Methods: This was a single institute, retrospective, case control study. A total of 45 patients were enrolled in this study. The predisposing factors, management, and prognosis of acute carotid blowout syndrome were evaluated. Results: Among the baseline characteristics, the site of the primary tumor (P =.003), origin of bleeding (P =.048), method of intervention (P =.005), and time to intervention (P =.006) were significantly different factors between survivor and nonsurvivor patients. After 24 hours of onset, a Glasgow Coma Scale score (P =.000), the use of inotropic agents (P =.007), and neutrophil-to-lymphocyte ratio (P =.019) were significantly predicting factors for outcome. Multivariate logistic regression analyses revealed bleeding from common carotid artery was an independent factor for long-term survival (odds ratio, 25.951; 95% confidence interval [CI], 1.373-490.441; P <.030). The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P =.092). Conclusions: Early and aggressive intervention is important for the successful management of acute carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were predictive factors for patients' outcomes. Bleeding from common carotid artery is an independent prognostic factor in multivariate analysis. Long-term survival can be achieved after successful management.