Abstract: OBJECTIVE To analyze the risk factors for influenza A virus infection in elderly patients with comorbidities, and to provide a basis for the early clinical screening of high-risk individuals. METHODS We retrospectively enrolled a total of 418 patients aged ≥65 years who were hospitalized in the infectious diseases department of the First Affiliated Hospital of Jinzhou Medical University from Jan. 2022 to Dec. 2024, including 211 patients with influenza A and 207 patients without influenza A infection. Data on patients' basic information, previous diseases, number of comorbidities, laboratory indicators and clinical manifestations were collected. Baseline variables prior to infection were included, and univariate analysis and multivariate logistic regression were employed to screen for risk factors for influenza A infection. RESULTS Univariate analysis showed that age ≥75 years, diabetes mellitus, chronic obstructive pulmonary disease (COPD), coronary heart disease, chronic kidney disease, use of immunosuppressants and Charlson Comorbidity Index (CCI) ≥3 were significantly associated with influenza A infection (P<0.05). Multivariate logistic regression analysis further confirmed that age ≥75 years (OR=2.402, 95%CI: 1.506-3.832), diabetes mellitus (OR=1.937, 95%CI: 1.257-2.984), COPD (OR=2.661, 95%CI: 1.682-4.210) and CCI ≥3 (OR=3.277, 95%CI: 2.097-5.121) were risk factors for influenza A infection. CONCLUSIONS Advanced age, diabetes mellitus, COPD and high comorbidity burden are risk factors for influenza A infection in elderly patients with comorbidities. The identification of these risk factors can provide a reference basis for the early clinical screening of high-risk individuals and the optimization of prevention and control strategies.