Staged total aortic replacement (TAR) is standard for patients with mega-aortic syndrome (MAS) and severe comorbidities, but a single-stage approach may be better for younger and fit patients. This report described the mid-term results of this approach. We conducted a retrospective medical chart review of all MAS patients in our center between May 2016 and December 2020 to analyze outcomes of single-stage TAR. Primary endpoints were mortality and major adverse postoperative events; secondary endpoints included aortic re-intervention, all complications, and survival. Of 47 MAS patients, 13 (27.7%) received single-stage TAR from valve to bifurcation through thoracophrenolumbotomy using circulatory arrest, antegrade cerebral and visceral perfusion. Mean age was 40.1±6.5 years. In-hospital mortality was 15.4%; two patients died on postoperative day (POD) 14 due to fatal stroke and POD 85 due to prosthesis infection. Mean intensive care stay was 7 (15) day, mean hospital stay was 27.5±16.2 day. Stroke occurred in two patients with "shaggy" aortas (one fatal, one transient); paraplegia in one; temporary acute renal failure in two (15.4%), and respiratory failure in 4 (30.8%). There was no aortic re-intervention or further mortality during follow-up. Total aortic replacement from valve to bifurcation is a safe approach for younger and fit patients with MAS and provides acceptable midterm outcomes in an experienced center. Thoracoabdominal incision at fourth intercostal space with retroperitoneal approach of abdominal aorta provides satisfactory exposure for the thoracic aorta and TAA and minimizes surgical trauma in comparison with a combination of two surgical incision.