Data on failure to rescue (FTR) after esophagectomy are sparse. We sought to better understand the patient factors associated with FTR and to assess whether FTR is associated with hospital volume. We identified all patients undergoing esophagectomy between 2010 and 2014 from the Agency for Healthcare Research and Quality Nationwide Readmission Database. We defined FTR as mortality after a major complication. Multiple logistic regression was used to identify patient factors and hospital-volume associations with FTR. Of 26,820 patients undergoing an esophagectomy, 7130 (26.6%) experienced a major complication. Of those, 1321 did not survive the index hospitalization (FTR rate, 18.5%). Risk factors for FTR included increasing age (adjusted odds ratio aOR, 1.06; P < .001), congestive heart failure (aOR, 2.07; P < .001), bleeding disorders (aOR, 2.9; P < .001), liver disease (aOR, 2.37; P = .001), and renal failure (aOR, 2.37; P = .002). At the hospital level there was wide variation in FTR rates across hospital volume quintiles, with 21.2% of patients suffering a complication not surviving to discharge at low-volume hospitals compared with 13.4% at high-volume hospitals (P < .001). At low-volume hospitals the highest FTR rates were acute renal failure (35.3%), postoperative hemorrhage (31.9%), and pulmonary failure (28.1%). One in 5 esophagectomy patients suffering a complication at low-volume hospitals do not survive to discharge. Several patient factors are associated with death after a major complication. Strategies to improve the recognition and management of complications in at-risk patients may be essential to improve outcomes at low-volume hospitals.