Background: Gastric ischemic conditioning prior to esophagectomy can increase neovascularization of the new conduit. Prior studies of ischemic conditioning have only investigated reductions in anastomotic leaks. Our aim was to analyze the association between gastric conditioning and all anastomotic outcomes as well as overall morbidity in our cohort of esophagectomy patients. Methods: We performed a retrospective review of patients undergoing esophagectomy from 2010 to 2015 in a National Cancer Institute designated center. Ischemic conditioning (IC) was performed on morbidly obese patients, those with cardiovascular disease or uncontrolled diabetes, and those requiring feeding jejunostomy and active tobacco users. IC consisted of transection of the short gastric vessels and ligation of the left gastric vessels. Primary outcomes consisted of all postoperative anastomotic complications. Secondary outcomes were overall morbidity. Results: Two-hundred and seven esophagectomies were performed with an average follow-up of 19 months. Thirty-eight patients (18.4%) underwent conditioning (IC). This group was similar to patients not conditioned (NIC) in age, preoperative pathology, and surgical approach. Five patients in the ischemic conditioning group (13.2%) and 57 patients (33.7%) in the NIC experienced anastomotic complications (p = 0.011). Ischemic conditioning significantly reduced the postoperative stricture rate fourfold (5.3 vs. 20.7% p = 0.02). IC patients experienced significantly fewer complications overall (36.8 vs. 56.2% p = 0.03). Conclusions: Gastric ischemic conditioning is associated with fewer overall anastomotic complications, fewer strictures, and less morbidity. Randomized studies may determine optimal selection criteria to determine whom best benefits from ischemic conditioning.