BACKGROUND/OBJECTIVES: Inadvertent intraoperative hypothermia is a common occurrence during major surgery, and some preclinical studies have reported its association with postoperative anastomotic leakage (AL). In the present study, we demonstrated the correlation between intraoperative hypothermia and postoperative outcomes after Ivor Lewis (IL) esophagectomy for cancer. METHODS: Retrospectively, patients were divided into three groups on the basis of their time-weighted average temperatures (TWA): normothermia (N-TWA 36-37.5 °C), mild hypothermia (M-TWA 35-36 °C), and severe hypothermia (S-TWA < 35 °C). RESULTS: Starting from 254 consecutive patients, 95 were included in the final analysis, classified according to intraoperative temperature: S-TWA = 19 (20%), M-TWA = 62 (65.3%), and N-TWA = 14 (14.7%). S-TWA was related to lower BMI ( = 0.001), diagnosis of squamous cell carcinoma ( = 0.029), and shorter operation times ( = 0.006). In the same way, AL was more related to S-TWA when compared with M-TWA and N-TWA (31.6% vs. 6.5% vs. 14.3%, = 0.015). After multivariate analysis, S-TWA remained as the only predictive factor of AL (OR 5.385, 95%CI 1.502; 19.310; = 0.010). Instead, higher BMI was found to be a protective factor for S-TWA (OR 0.818, 95%CI 0.723; 0.926: = 0.001). CONCLUSIONS: S-TWA seems to be a major independent risk factor for AL after IL esophagectomy. Implementation of perioperative measures, aimed to prevent severe intraoperative hypothermia, could potentially be crucial to improve surgical outcomes.