Objective To explore risk factors and prevention and control measures of healthcare-associated infection(HAI) in hospitalized patients with chronic obstructive pulmonary disease (COPD). Methods A retrospective analysis on HAI in hospitalized patients with COPD in department of respiratory medicine of a tertiary hospital from July 1, 2014 to June 30, 2017 was conducted, 1:1 HAI case and non-infectious case was matched, risk factors were analyzed by univariate chi-square test and multivariate logistic regression analysis. Results A total of 1 499 COPD patients were investigated, 118 cases of HAI occurred, and all matched cases were found, HAI rate and HAI case rate were 7.87% and 8.27% respectively. Univariate analysis showed that risk factors for HAI in COPD patients were recent stay in intensive care unit(ICU), severe or extremely severe pulmonary function grading, malignant tumor, combined with other pulmonary diseases, indwelling urinary catheter, indwelling central venous catheter, antimicrobial use time>14 days, antimicrobial use>2 kinds, non-invasive ventilation, and hypoproteinemia, diffe-rences were all statistically significant (all P<0.05). Multivariate logistic analysis showed that there were 6 independent risk factors for HAI in COPD patients:pulmonary function grading, malignant tumor, combined with other pulmonary diseases, antimicrobial use>2 kinds, hypoproteinemia, and non-invasive ventilation. Conclusion Health care workers should rationally use antimicrobial agents, actively treat complications, strengthen nutritional support, pay attention to the evaluation of pulmonary function, master the best weaning time of non-invasive ventilator and implement disinfection, so as to reduce the incidence of HAI in COPD patients.