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Thoracoscopic esophagectomy (TE) in the prone position for patients with esophageal cancer has received a great deal of attention. We retrospectively compared clinical outcomes and surgical stress of TE in the prone position (TE-P) and in the lateral position (TE-L) at our institution.A total of 58 consecutive patients (28 in the TE-L group and 30 in the TE-P group) were studied. Between the 2 groups, clinical outcomes and various parameters were compared.There were no hospital deaths in both TEL and TEP groups. Blood loss during the thoracoscopic part of the surgery were significantly (P<0.01) lower in the TE-P group (118±72 mL) compared with the TE-L (245±203 mL) group. The incidence of respiratory complications tended to be lower (P=0.07) in the TE-P group (3.3%) than in the TE-L (17.8%) group. The duration of systemic inflammatory response syndrome condition was significantly (P=0.02) shorter in the TE-P group (1.5±2.5 d) than in TE-L (3.6±3.5 d) group. The levels of serum C-reactive protein on postoperative days 1 and 2 were significantly (P<0.01) lower in the TE-P group than in the TE-L group.TE-P for patients with esophageal cancer was safe and feasible. TE-P might be a potentially less invasive procedure than TE-L.