Abstract Delayed gastric emptying (DGE) after esophagectomy is not uncommon and would significantly impair patient’s quality of life. Risk factors of DGE remained poorly understood. This study aimed to assess this unresolved issue. We performed a retrospective study in patients with esophageal cancer who underwent esophagectomy and reconstructed with the gastric substitute between 2000 to 2020. DGE was defined as less than 50% emptying of the contrast medium within 10 minutes on postoperative esophagography. Multivariable logistic analysis was performed to identify patient-, tumor- and procedure-related factors that increase the risk of DGE. Among 810 eligible patients, the incidence of DGE was 12.2%. Patients who developed DGE had higher incidence of pneumonia (23.2% vs. 10.7%, p < 0.001), longer hospital stay (25.16vs.19.89 days, p < 0.001), and higher rate of in-hospital mortality (4% vs. 1%, p = 0.014). Multivariate analysis identified pre-existing COPD (OR, 2.38; p = 0.004), whole stomach reconstruction (vs. gastric tube, OR, 6.96; p = 0.001) and posterior mediastinum route (vs. retrosternum, OR, 5.35; p = 0.002) as independent risk factors for DGE. The incidence of DGE was 0.6% in patients who received gastric tube reconstruction via retrosternum route as opposed to 20.6% who received whole stomach reconstruction via posterior mediastinum route. DGE after esophagectomy is associated with increased morbidity and mortality. Type of gastric conduit and route of reconstruction played important roles in the development of DGE.