Left ventricular assist device (LVAD) implantation via left lateral thoracotomy with outflow cannula anastomosis to the descending aorta is an alternative technique that avoids anterior mediastinal planes and requires a single incision. This study compares changes in exercise capacity following LVAD implantation with outflow cannula anastomosis to the descending aorta versus ascending aorta. Adult patients who received a continuous flow centrifugal LVAD implantation and completed both pre- and postimplantation cardiopulmonary exercise tests (CPETs) and or 6-minute walk tests (6MWT) were included. Change in CPET parameters (maximum oxygen intake: vO(2)max, oxygen uptake efficiency ratio: OUES, ventilatory efficiency ratio: vE/vCO(2)Slope) and 6MWT distance were compared between ascending and descending aorta anastomosis groups. Ascending and descending aorta anastomosis cohorts included 59 and 14 patients, respectively. Pre- and postimplantation CPETs were performed 63 +/- 12 days before and 216 +/- 17 days following implantation. The improvement in CPET parameters (vO(2)max, OUES, vE/vCO(2)Slope) or 6MWT distance was not significantly different between the ascending and descending aorta anastomosis groups. This study found no significant difference in the improvement of CPET parameters or 6MWT distance between LVAD implantation via thoracotomy with outflow cannula anastomosis to descending aorta and standard implantation via sternotomy with outflow cannula anastomosis to ascending aorta.