Abstract: Objective To investigate the clinical efficacy and safety of early awake prone ventilation therapy in patients with stroke-associated pneumonia (SAP). Methods Cluster sampling was used in the study. A total of 78 patients with acute ischemic stroke complicated by pneumonia who were admitted to Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, from June 2023 to June 2025 were enrolled. The patients were randomly divided into a control group and a test group. The control group received routine treatment and nursing care, while the test group received early awake prone ventilation in addition to the routine regimen. Both groups were treated for one week. Pulmonary CT quantitative indices (mean CT value of the whole lung; ventilation-deficient lung and well-aerated lung volumes and their ratio), the minimum oxygen saturation (SpO₂) before treatment and on days 1, 3, and 7 after treatment, inflammatory markers (high-sensitivity C-reactive protein, procalcitonin, and white blood cell count), and length of hospitalization stay were compared between the two groups. The incidence of complications was also recorded for prognostic evaluation. Results There were no statistical differences in baseline data between the two groups (P>0.05). After treatment, the test group showed significant decreases in mean whole-lung CT value than the control group, decreases in the volume and volume ratio of ventilation-deficient lung, and increases in the volume and volume ratio of well-aerated lung (P<0.05). The minimum SpO₂ values on days 1, 3, and 7 after treatment were higher in the test group than in the control group (P<0.05). Inflammatory marker levels on days 3 and 7 after treatment were significantly lower in the test group than in the control group (P<0.05). The length of hospitalization stay was shorter in the test group than in the control group (P<0.05). There was no statistical difference in the incidence of complications between the two groups (P>0.05). Conclusions Early awake prone ventilation can effectively improve pulmonary ventilation in SAP patients, alleviate pulmonary inflammatory responses, increase oxygen saturation, and shorten the length of hospitalization stay, with good safety, and is therefore worthy of clinical promotion.