Background/Aims: Anastomotic leakage (AL) after esophagectomy is associated with high rates of postoperative morbidity and mortality. In cases with leakage, a refractory fistula (RF) is sometimes recognized after esophagectomy. The aim of this study was to evaluate the risk factors for RF after esophagectomy with gastric tube reconstruction. Methods: This study enrolled 244 consecutive esophageal cancer patients who had undergone esophagectomy with gastric tube reconstruction. RF was defined as a noncurative anastomotic site-cutaneous fistula that had been present for more than 2 months. We evaluated the risk factors for RF. Results: AL occurred in 30 patients (12.3%). There was one mortality case (0.4%) due to mediastinitis caused by AL in the present series. A multivariate analysis revealed that the subcutaneous route was an independent risk factor for AL (OR 4.42, 95% CI 1.42-13.8, p = 0.01), and that the subcutaneous route was an independent risk factor for RF (OR 13.30, 95% CI 2.50-71.30, p = 0.0024). Conclusion: The results of this retrospective study suggest that subcutaneous route was associated with an increased risk of RF after esophagectomy with gastric tube reconstruction. The preoperative identification of risk factors may contribute to the prevention of postoperative AL and RF.