Abstract: Objective To evaluate the feasibility and safety of combined laparoscopic and thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis for the treatment of esophageal cancer. Methods We retrospectively analyzed clinical data of 40 patients with esophageal cancer who underwent esophagectomy in Beijing Chaoyang Hospital of Capital Medical University from March 2010 to March 2012. All the 40 patients were divided into 2 groups according to their different surgical approach， including 22 patients who underwent combined laparoscopic and thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis （minimally invasive surgery group） and 18 patients who underwent Ivor Lewis esophagectomy （open surgery group）. Operation time， intra-operative blood loss， lymph node dissection， postoperative morbidity， hospital stay and cost were compared between the two groups. Results The hospitalcost of minimally invasive surgery group was significantly higher than that of open surgery group ［（78 181.5±8 958.8） yuan vs. （61 717.2±35 159.4） yuan， Z=4.078，P=0.000］ . There was no statistical difference in operation time ［（292.0±74.8） min vs. （256.1±41.0） min， t=1.838，P=0.074］， intra-operative blood loss ［（447.7±597.0） ml vs. （305.6±125.9） ml， Z=0.401，P=0.688］， total number of dissected lymph nodes （230 vs. 215， t=1.714，P=0.095）， postoperative morbidity ［22.7% （5/22） vs. 33.3% （6/18）， χ2=0.559，P=0.498］， time to resume oral intake ［（8.5±3.5） d vs. （11.1±9.6） d，t=1.202，P=0.237］， and postoperative hospital stay ［（11.6±5.7） d vs. （13.3±9.4） d， t=0.680， P=0.501）］ between the two groups. The minimally invasive surgery group was further divided into two subgroups according to operation date， including 10 patients in the early stage subgroup and 12 patients in the later stage subgroup. The operation time of the later stage subgroup was significantly shorter than that of the early stage subgroup ［（262.9±64.9） min vs. （327.5±73.0） min， t=2.197， P=0.040］， but not statistically different from that of the open surgery group ［（262.9±64.9） min vs. （256.1 ±41.0） min， t=0.353， P=0.727］. Intra-operative blood loss of the later stage subgroup was significantly reduced compared with those of the early stage subgroup ［（220.8±149.9） ml vs. （720.0±808.0） ml， Z=3.279， P=0.001)］ and the open surgery group ［（220.8±149.9）ml vs. （305.6±125.9） ml， Z=2.089， P=0.037）］. Conclusion Combined laparoscopic and thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis is a safe and effective surgical procedure for the treatment of esophageal cancer.