Background: Esophageal cancer is the sixth-most common cause of cancer-related death worldwide. Surgery is the gold standard treatment for resectable esophageal cancer, and McKeown esophagogastrectomy-one of the most frequently performed operations in these cases-is often associated with severe postoperative infection. Aim: To analyze the risk factors of postoperative infection in patients who have undergone McKeown esophagogastrectomy. Methods: We retrospectively investigated the clinical data of 428 patients who have undergone McKeown esophagogastrectomy, and divided them into infection and non-infection groups. Data were analyzed using SPSS 22.0 software. Results: Between the infection and non-infection groups, smoking status (66.7% vs. 49.2%; P=0.007), male gender (86.1% vs. 74.7%; P=0.037), hoarseness (23.6% vs. 12.4%; P=0.013), poor coughing ability (51.4% vs. 13.2%; P<0.001), preoperative white blood cell (WBC) count (7.64 +/- 2.86x10(9)/L vs. 7.04 +/- 2.27x10(9)/L; P=0.049), postoperative day 1 (POD1) WBC count (13.24 +/- 4.98x10(9)/L vs. 11.53 +/- 4.15x10(9)/L; P=0.03), POD1 neutrophil count (11.84 +/- 4.73x10(9)/L vs. 10.24 +/- 3.87x10(9)/L; P=0.02), POD1 serum albumin (ALB) level (29.46 +/- 6.41 g/L vs. 31.76 +/- 3.64 g/L; P=0.000), POD1 creatine level (CRE; 78.15 +/- 24.09 mu mol/L vs. 70.74 +/- 20.92 mu mol/L; P=0.008), and POD1 blood glucose levels (11.45 +/- 4.39 mmol/L vs. 9.38 +/- 3.21 mmol/L; P=0.000) were significantly different. These factors were assessed using logistic regression analysis, and factors with P=0.05 in the univariate analysis were entered into multivariate analysis based on the forward stepwise (conditional) method. Poor coughing ability (odds ratio [OR], 6.916, 95% confidence interval [CI], 3.716-12.871), smoking status (OR, 2.434; 95% CI, 1.299-4.563), POD1 WBC count (OR, 1.113; 95% CI, 1.040-1.191), POD1 serum ALB level (OR, 0.821; 95% CI, 0.752-0.897), and POD1 blood glucose levels (OR, 1.093; 95% CI, 1.005-1.187) were determined as independent risk factors for postoperative infection. We established a scoring system based on these 5 factors, and the area under the curve for this predictive model was 0.792 (range, 0.736-0.848); the sensitivity, specificity, and cut-off score were 73.6%, 73.0%, and 2.5, respectively. Conclusion: Among patients who have undergone McKeown esophagogastrectomy, poor coughing ability, smoking habit, high WBC and blood glucose levels, and low serum ALB levels can be used to predict the occurrence of postoperative infections.