Background Compared with open oesophagectomy (OE), minimally invasive oesophagectomy (MIO) proves to have benefits in reducing the risk of pulmonary complications for patients with resectable oesophageal cancer. However, it is unknown whether MIO has superiority in reducing the occurrence of in-hospital mortality (IHM). Objective The objective of this meta-analysis was to explore the effect of MIO vs. OE on the occurrence of in-hospital mortality (IHM). Data Sources Sources such as Medline (through December 31, 2014), Embase (through December 31, 2014), Wiley Online Library (through December 31, 2014), and the Cochrane Library (through December 31, 2014) were searched. Study Selection Data of randomized and non-randomized clinical trials related to MIO versus OE were included. Interventions Eligible studies were those that reported patients who underwent MIO procedure. The control group included patients undergoing conventional OE. Study Appraisal and Synthesis Methods Fixed or random-effects models were used to calculate summary odds ratios (ORs) or relative risks (RRs) for quantification of associations. Heterogeneity among studies was evaluated by using Cochran's Q and I-2 statistics. Results A total of 48 studies involving 14,311 cases of resectable oesophageal cancer were included in the meta-analysis. Compared to patients undergoing OE, patients undergoing MIO had statistically reduced occurrence of IHM (OR=0.69, 95%CI = 0.55-0.86). Patients undergoing MIO also had significantly reduced incidence of pulmonary complications (PCs) (RR=0.73, 95%CI = 0.63-0.86), pulmonary embolism (PE) (OR=0.71, 95%CI = 0.51-0.99) and arrhythmia (OR=0.79, 95%CI = 0.68-0.92). Non-significant reductions were observed among the included studies in the occurrence of anastomotic leak (AL) (OR=0.93, 95%CI = 0.78-1.11), or Gastric Tip Necrosis (GTN) (OR=0.89, 95%CI = 0.54-1.49). Limitation Most of the included studies were non-randomized case-control studies, with a diversity of study designs, demographics of participants and surgical intervention. Conclusions Minimally invasive oesophagectomy (MIO) has superiority over open oesophagectomy (OE) in terms of the occurrence of in-hospital mortality (IHM) and should be the first-choice surgical procedure in esophageal surgery.