For patients with esophageal cancer, radical surgical resection of the esophagus and surrounding lymph nodes is the only curative treatment option. The conventional open esophagectomy has the disadvantage of extensive trauma and slow recovery. Recently, video-assisted thoracoscopic surgery (VATS) has been applied in esophagectomy, and it appears to have better outcome preliminarily. In this study, we compared the short-term quality of life (QOL) in patients with esophageal cancer after subtotal esophagectomy via VATS or open surgery. A total of 56 patients who underwent three-incision esophagectomy by the same surgical group from January 2007 to February 2008 were enrolled in this retrospective study. Twenty-seven patients followed VATS (VATS group) and 29 patients followed open surgery (open group). The EORTC core questionnaire (QLQ C-30) together with esophageal-specific module (OES-18) were applied to assess the short-term QOL of the patients before and 2, 4, 16, 24 weeks after operation. In result, all of the global quality scale, functioning scale, general symptom scales (or items) did not show differences before operation between the two groups. Further, the scores of global quality and physical functioning were higher in VATS group than in open group overall after operation, however, the scores of fatigue, pain, dyspnea were lower inversely. In conclusion, VATS shows an overall benefit on QOL for the patients with esophageal cancer during the follow-up of six month after esophagectomy, compared with open surgery.