Objective To assess the efficacy of the trans-cervical and trans-hiatal esophagectomy versus thoracoscopic esophagectomy in patients with esophageal carcinoma. Methods A total of 80 esophageal carcinoma patients undergoing surgical treatment in our hospital from September 2018 to October 2020 were enrolled in this study, and they were divided into observation group (n=40) and control group (n=40). The patients out of the observation group underwent the trans-cervical and trans-hiatal esophagectomy, and those from the control group underwent the thoracoscopic esophagectomy. The preoperative, intraoperative and postoperative data were analyzed between the 2 groups, regarding intraoperative blood loss, number of dissected mediastinal lymph nodes, operation time, number of lymph nodes in left para-recurrent laryngeal nerve (para-RLN) or right para-RLN, length of staying in intensive care unit (ICU), postoperative pain score, length of postoperative stay, PO2/fraction of inspiration O2 (PO2/FIO2), pulmonary infection, and lymphatic metastasis. Results The operation was successfully performed in all 80 patients. The patients in the observation group had shorter operation time (200 vs 235 min, Z=-3.700, P < 0.001) and larger number of dissected mediastinal lymph nodes in left para-RLN (25.0% vs 2.5%, Z=2.568, P=0.010) than those in the control group. Significant differences were observed in the pain scores of postoperative day 1 (0% vs 17.5%, Z=-4.292, P < 0.001) and day 3 (12.5% vs 37.5%, Z=-3.363, P < 0.001), postoperative 48-h PO2/FIO2 (290 vs 255 min, Z=3.747, P < 0.001), length of postoperative stay (7 d vs 8 d, Z=-2.119, P=0.034), and incidence of postoperative pulmonary infection (χ2=4.114, P=0.043) between the 2 groups. Conclusion Trans-cervical and trans-cervical esophagectomy is a good approach in treatment of esophageal carcinoma, and may provide an option to the patients who cannot suffer from the thoracotomy.