Although cerebrospinal fluid drainage has been shown to reduce the risk of ischemic spinal cord injury, serious complications have also been reported. We have been using it selectively in a pressure- and volume-regulated method and aimed to evaluate its safety, and its validity in elective thoracic endovascular aortic repair in a propensity-matched cohort. Among the 450 patients who underwent open surgery (n = 169) or thoracic endovascular aortic repair (n = 281) on the descending or thoracoabdominal aorta, 147 underwent cerebrospinal fluid drainage, which was prophylactic in 135 and therapeutic in 12. Prophylactic drainage was performed in elective open surgery under distal aortic perfusion (n = 67) or in selected patients undergoing thoracic endovascular aortic repair (n = 68). Drainage-related complications were observed in 13 (9.6%), one of which was graded severe (0.74%). In patients undergoing prophylactic drainage, spinal cord injury was detected in 2/135 (1.5%). In patients without prophylactic drainage, 15/315 (4.8%) developed spinal cord injury. Therapeutic drainage was performed in 12 of these 15 patients, 10 of whom remained paralytic in varying degree. In the inverse probability weighted analysis of the patients undergoing elective thoracic endovascular aortic repair, the incidence of spinal cord injury was lower with prophylactic drainage (p = 0.028). Pressure- and volume-regulated spinal drainage rarely causes serious complications. Its prophylactic use seems beneficial in selected patients, including those undergoing thoracic endovascular aortic repair with high risk for spinal cord injury.