Objective To assess the disease burden and risk factors of healthcare-associated infection(HAI) caused by Stenotrophomonas maltophilia(S. maltophilia) in intensive care unit (ICU). Methods Patients with HAI caused by S. maltophilia in general ICU of Xiangya Hospital of Central South University from January 1 to December 31, 2017 were collected as case group, each case was matched with 2 non-infected patients of the same gender and age difference ≤ 3 years old as control group. Data about demographic information, disease severity, length of hospital stay, hospitalization expense, underlying diseases, invasive operations, and antimicrobial use were collected, risk factors were analyzed by logistic regression analysis. Results Incidence and case incidence of S. maltophilia HAI in ICU were 1.47% (29/1 973) and 1.57% (31/1 973) respectively. Duration from admission to infection was (17.86±16.51)days, duration from admission in ICU to infection was(7.34±9.12)days. The main infection site was lung (74.19%). Length of hospital stay and ICU stay, hospitalization expenses and antimicrobial expenses of case group were all higher than control group, while cure rate was lower than control group. Susceptibility rate of S. maltophilia to compound sulfamethoxazole and minocycline was more than 90%, while non-susceptibility rate to cefoperazone/sulbactam was more than 75%. In case group, 82 strains of other bacteria were isolated from 27 (93.10%) clinical specimens, including 59 strains (71.95%)of multidrug-resistant organisms; 13 strains of fungi were isolated from 10 cases of infection (34.48%). Univariate analysis showed that patients in case group were with older age, high proportion of males, long length of ICU stay, higher APACHE Ⅱ score and fasting blood sugar, lower hemoglobin, high proportion of mechanical ventilation, central venous catheterization, fiberoptic bronchoscopy, blood purification treatment, blood transfusion, chemotherapy, cephalosporins and enzyme inhibitors, penicillins+enzyme inhibitors, carbapenems, quinolones and glycopeptides treatment. Multivariate logistic analysis showed that the use of cephalosporins+enzyme inhibitors, carbapenems and glycopeptides were independent risk factors for S. maltophilia HAI. Conclusion S. maltophilia HAI mostly occurrs in patients with old age, serious illness, long length of hospital stay and use of broad-spectrum antimicrobial agents, it is necessary to strengthen surveillance, prevention and control. The burden of S. maltophilia HAI in ICU patients is heavy, antimicrobial resistance is increasing.