Abstract Background Esophageal cancer was the ninth most common malignant tumor and ranked sixth for death globally, especially in developing country[1]. Standardized esophagectomy followed by chemotherapy or chemoradiotherapy remains the curative treatment for esophageal cancer[2]. Ivor Lewis esophageal resection, including two-stage approach for carcinoma of the middle third of the esophagus, was proposed in 1946[3]. Meanwhile, to avoid the risk of anastomotic leakage in Ivor Lewis surgery, three-stage approach with cervical anastomosis was introduced by McKeown[4]. However, considering the less complications of minimally invasive Ivor Lewis esophagectomy and the increased incidence of distal esophageal and gastroesophageal junction adenocarcinoma, two-stage approach with intrathoracic anastomosis was gaining more attention. Recent years, thoracoscopic laparoscopic esophagectomy with intrathoracic anastomosis (TLE-chest) has gradually become the mainstream approach of minimally invasive Ivor Lewis esophagectomy for the treatment of middle and lower esophageal cancers. In the previous study, we described the technique strategies of TLE-chest, which was featured with improved anastomosis layer by layer and embedding of the anastomosis with preserved mediastinal pleura[5]. In this study, we presented the perioperative data, complications and long-term survivals of TLE-chest in esophageal cancers. Methods The clinical data of 201 patients, who underwent TLE-chest for primary esophageal cancer in the First Affiliated Hospital of Anhui Medical University (FAHAMU) from November 2011 to December 2015, was analyzed retrospectively. Postoperative patients’ life quality by the European Organization into Research and Treatment of Cancer (EORTC) quality of life questionnaire for esophageal cancer and overall survivals were analyzed using Kaplan–Meier curve. The normal distribution of the measured data is expressed in terms of x ± s. Cox's hazard regression model was used for single factor and multi-factor analysis. Results Overall, 168 (83.6%) patients were males and 33 (16.4%) were females. The mean age of patients was 62.7 years old (range from 40 to 88). 150 (74.6%) patients’ tumors were located in the middle of esophagus, whereas 50 (24.9%) and 1 (0.5%) tumors were in the low and up. 194 (96.5%) esophageal tumors were confirmed as squamous carcinoma expect 7 (3.5%) adenocarcinomas. The mean of tumor size was 3.7 cm and the numbers of postoperative pathological TNM classification I, II, III and IV were 38 (18.9%), 72 (35.8%), 73 (36.3%) and 18 (9%) respectively. The average of total operation time was 293.9 min. Among them, the means of VATS and LS time were 156.9 min and 116.5 min respectively. The mean of intraoperative blood loss was 77.5 ml. The number of resected lymph nodes was 22.9 ± 9.7 (maximum: 58).7 (3.5%) patients suffered from anastomotic fistula, 5 (2.5%) patients occurred RRLN injury in lymph nodes dissection and 5 (2.5%) suffered chylothorax. Pulmonary complications were observed in 21 (10.4%) patients. Meanwhile, the rates of other complications containing anastomotic stenosis, bleeding and delayed gastric empty were 0.5% (1/201), 1.5% (3/201) and 0.5% (1/201) respectively. The score of quality of patients’ life was 85 ± 6.5. And at the 12 months, quality of life was improved by 4.1%. Until up to the 24 months, patients’ quality of life was recovered to 90 ± 7.5. The 1, 2 and 3 years overall survival of 100 patients was 94%, 79% and 74% respectively. Univariate analysis showed that the pT stage (P = 0.040), pN stage (P = 0.001), pTNM stage(P = 0.001) and Total operative time(P = 0.000) were associated with 3-year overall survival (3-OS). Further, multivariate analysis affirmed that the operative time (≥ 311 min), tumor size (≥ 3.5 cm) and pTNM stage were independent prognostic factors for 3-OS (P < 0.05). Conclusion TLE-chest surgery in esophageal cancer was safe and effective. And the total operative time, tumor size and TNM stage could be used as independent prognostic indicators in esophageal cancer patients after the TLE-chest. Disclosure All authors have declared no conflicts of interest.