Objective To summarize the distribution characteristics of healthcare-associated infection (HAI) after esophageal cancer surgery, analyze the relevant risk factors for HAI, provide reference for reducing HAI after esophageal cancer surgery, and improve patients' life quality. Methods Clinical data of patients with esophageal cancer who underwent surgery in a hospital from January to December 2022 were analyzed retrospectively. Postope-rative HAI sites and distribution were summarized. Chi-square test, univariate analysis and multivariate analysis were adopted to conduct correlation analysis on the basic characteristics, surgery-related influencing factors, antimicrobial use, risk factors and the occurrence of HAI in patients during hospitalization period. Results A total of 404 patients underwent esophageal cancer surgery were included in the analysis, among which 102 cases had 118 episodes of HAI, leading to an incidence and a case incidence of HAI of 25.25% and 29.21% respectively. The major infection sites were lower respiratory tract (n=57, 48.31%), pleural cavity (n=31, 26.27%), and organ space (n=16, 13.56%). Multivariate logistic regression analysis showed that age ≥60 years (OR=2.115, 95%CI: 1.150-3.890), length of hospital stay ≥25 days (OR=8.388, 95%CI: 4.491-15.667) and duration of postope-rative antimicrobial use ≥10 days (OR=2.885, 95%CI: 1.506-5.527) were independent risk factors for the occurrence of postoperative HAI (all P<0.05). Conclusion The major HAI in patients after esophageal cancer surgery is lower respiratory tract infection, and is caused by multiple factors. Patients aged ≥60 years, with a length of hospital stay ≥25 days, and duration of postoperative antimicrobial use ≥10 days are more likely to develop postoperative HAI. In order to improve the life quality of patients underwent esophageal cancer surgery, it is recommended to further strengthen perioperative management, optimize the nursing quality for patients during hospitalization, and use antimicrobial agents rationally to reduce the occurrence of HAI.