Objective To investigate the predictive value of preoperative plasma total cholesterol levels for postoperative delirium （POD） following esophagectomy and to analyze its associated risk factors. Methods The complete perioperative electronic medical records of 187 patients with POD who underwent esophagectomy at the 960 Hospital of the People's Liberation Army between January 2019 and December 2023 were retrospectively analyzed. According to the occurrence of POD within one week postoperatively， the patients were categorized into a delirium group and a non?delirium group. The preoperative plasma total cholesterol levels were used to construct a receiver operating characteristic （ROC） curve for predicting delirium after esophagectomy. The area under the curve （AUC） and its 95% confidence interval （CI） were calculated. Additionally， the plasma total cholesterol level corresponding to the maximum Youden index （sensitivity + specificity?1） was determined as the optimal critical value. Results POD occurred in 24 of 187 patients who underwent esophageal cancer resection， with an incidence rate of 12.83%. Compared to the non?delirium group， the delirium group exhibited older age， lower intraoperative blood pressure， lower plasma total cholesterol and low?density lipoprotein levels， longer anesthesia duration， and a higher prevalence of coronary heart disease， which was identified as a risk factor for POD. Dexmedetomidine administration was associated with a reduced occurrence of POD. The AUC， 95%CI， cut?off value， sensitivity， and specificity of preoperative plasma total cholesterol level for predicting POD were 0.761， 0.657 ~ 0.865， ≤ 4.11 mmol/L， 70.8%， and 77.3%， respectively. Conclusions Among non?hyperlipidemic patients， low preoperative plasma total cholesterol levels and intraoperative hypotension are identified as independent risk factors for POD following esophageal cancer resection. Preoperative plasma total cholesterol levels exhibit moderate predictive value for the occurrence of POD.