A single-center retrospective study reviewed 68 patients admitted to a hemorrhage unit for severe non-variceal upper gastrointestinal bleeding who underwent contrast-enhanced CT angiography to detect the status, etiology, and site of hemorrhage. Its performance was compared with the reference standards. The results demonstrated the highly significant sensitivity of contrast-enhanced CT angiography in identifying the etiology and site of bleeding. Therefore, contrast-enhanced CT angiography may play a crucial role in the diagnostic workup and management of acute and severe non-variceal upper gastrointestinal bleeding, also helping to select the type of treatment and guiding its timing.