One-lung ventilation (OLV) is the most commonly used ventilation strategy during esophagectomy. However, two-lung ventilation (TLV) with artificial pneumothorax has been applied in recent years during esophagectomy. It is unclear whether TLV takes advantages over OLV for esophagectomy. Here, we conducted a meta-analysis to compare the effects of TLV and OLV for esophagectomy. We searched relevant studies from the Cochrane Central Register of Controlled Trials, Pubmed, and Embase in November 2020. We included studies that compared the effects of TLV with OLV in esophagectomy and provided sufficient perioperative and postoperative data. We extracted data of postoperative outcomes (postoperative pulmonary complications, anastomotic leak, hospital stay) and surgical variables (thoracic phrase time, blood loss, the number of total resected thoracic lymph nodes). We calculated the risk ratio (RR) for dichotomous data and the weighted mean differences (WMDs) for continuous data. Six studies with 1725 patients were included in this meta-analysis. TLV was associated with significantly lower incidence of postoperative pulmonary complications [RR = 0.714; 95% confidence interval (CI) = (0.534, 0.956); P = 0.023], shorter hospital stay [WMD = - 0.148; 95% CI = (- 0.246, - 0.051); P = 0.003], less blood loss [WMD = - 0.352; 95% CI = (- 0.528, - 0.176); P < 0.001] and more resected thoracic lymph nodes [WMD = 0.207; 95% CI = (0.003, 0.4120); P = 0.047] than OLV. Moreover, TLV consumed similar time for thoracic phrase [WMD = - 0.289; 95% CI = (- 0.661, 0.083); P = 0.128], and yielded a comparable rate of anastomotic leak [RR = 1.086; 95% CI = (0.842, 1.400); P = 0.525] compared with OLV. TLV with artificial pneumothorax resulted in less trauma than OLV. TLV with artificial pneumothorax is safe and could be a choice of ventilation strategy for esophagectomy.