Background: Stroke is the second leading cause of death and third leading cause of death and disability combined in the world. The mortality of ischemic stroke is not known in TGSH despite it is one of a tertiary hospital in the region where most of stroke patients are referred from other tertiary, general and primary hospitals for further investigation and management. So, the aim of this study was to assess the magnitude of in-hospital mortality and its predic-tors. Objective: To assess in-hospital mortality and its predictors among adult acute ischemic stroke patients in TGSH, Bahir Dar, Northwest Ethiopia, 2026. Methods: Institution-based cross-sectional study was conducted from December 1-30, 2025 by reviewing medical records of ischemic stroke patients admitted from January 1, 2023 to December 30, 2025. The sample size was 244 and the sampling technique was simple random sampling. The data was collected from patient’s medical record by using kobo collect software, having pre-developed data collection check list through smartphone, then it was transferred to SPSS version 27 for analysis. Bi-variable and multi-variable logistic regression analysis was used to identify the predictors of ischemic stroke mortality. Results: In-hospital mortality of ischemic stroke was 13.8% (95% CI,9.5-18.1). Those pa-tients who had aspiration pneumonia have 3.80 times higher risk ofmortality (AOR=3.80, 95% CI (1.46-10.15)). Patients who had increased intracranial pressure have 5.61 times higher risk of mortality (AOR=5.61, 95% CI (2.28-16.83)). Patients who had associated MI at the same admission have 3.68 times higher risk of mortality (AOR=3.68, 95% CI (1.01-13.48)). Conclusion: In-hospital mortality of ischemic stroke was relatively high. The presence of Aspiration pneumonia, associated MI and increased ICP at time of admission were found to be significant predictors of in-hospital mortality for ischemic stroke patients. Early identifica-tion and treatment of complications and other co-morbidities along with strict follow-upin the hospital are required to reduce in-hospital ischemic stroke mortality and long-term disability.