Objective: The aim was to evaluate the best intra-thoracoscopic surgery technique between video-assisted thoracic surgery (VATS) combined with laparoscopy and right open transthoracic esophagectomy, in patients with esophageal cancer. Methods: From November 2006 to May 2008, 221 patients with esophageal cancer were enrolled in this study, prospective randomized in two groups. 111 patients were performed the VATS technique (Experimental group), whereas in the other 110 patients esophagectomy was adopted by thoracotomy (Control group). Results: The time consuming of Experimental group was 272.3 min in average with a standard deviation(std) of 57.9, and it was 218.7 min in average with std of 91.0 in the control group (P=0.000). The operative blood loss was 219.7±194.4 mL in the Experimental group, compared with 590.0±324.4 mL in the control group, with significant difference (P=0.000). Postoperative hospital stay of Experimental group was 9.6±1.7d, and it was 11.4±2.3d in the control group (P=0.000). There was no-delayed union of incision in the Experimental group, but 6.36% in the control group (P=0.007). The disorder of gastric emptying occurred 0.9% in the Experimental group, whereas 6.4% in the Control group. There was no significant difference in survival curves and rates (P=0.555). Conclusion: There were several advantages of VATS technique, such as reduced hemorrhage, better recovery, few complications, and great number of lymph node dissection, although there was no significant difference in long-term survival rate. Thus the VATS combined with laparoscopy technique was worthy of generalization in esophageal surgery with good prospects. Objective: The aim was to evaluate the best intra-thoracoscopic surgery technique between video-assisted thoracic surgery (VATS) combined with laparoscopy and right open transthoracic esophagectomy, in patients with esophageal cancer. Methods: From November 2006 to May 2008, 221 patients with esophageal cancer were enrolled in this study, prospective randomized in two groups. 111 patients were performed the VATS technique (Experimental group), but in the other 110 patients esophagectomy was adopted by thoracotomy (Control group). Results: The time consuming of Experimental Group was 272.3 min in average with a standard deviation (std) of 57.9 and it was 218.7 min in average with std of 91.0 in the control group (P = 0.000). The operative blood loss was 219.7 ± 194.4 mL in the Experimental group, compared with 590.0 ± 324.4 mL in the control group, with significant difference (P = 0.000). Postoperative hospital stay of Experimental group was 9.6 ± 1.7 days, and it was 11.4 ± 2.3 days in the control There was no-delayed union of incision in the Experimental group, but 6.36% in the control group (P = 0.007). The disorder of gastric emptying occurred 0.9% in the Experimental group, while 6.4% in the Control group. There was no significant difference in survival curves and rates (P = 0.555). Conclusion: There were several advantages of VATS technique, such as reduced hemorrhage, better recovery, few complications, and great number of lymph node dissection, there was no significant difference in long-term survival rate. Thus the VATS combined with laparoscopy technique was worthy of generalization in esophageal surgery with good prospects.