The purpose of this study was to identify predictors of in-hospital mortality after acute stroke and investigate the impact of gender on stroke mortality. All patients admitted to Al-watani governmental hospital in Palestine from September 2006 to August 2007 and diagnosed with acute stroke were included in the study. Diagnosis of stroke was confirmed by computerized tomography scan. Demographics and clinical data pertaining to the patients were obtained from their medical files. The main outcome measure in this study was vital status at hospital discharge. Multiple logistic regression analysis was used to identify the independent predictors of in-hospital mortality. Statistical analysis was carried out using SPSS 15.A total of 186 acute stroke cases (95 females and 91 males) were included in the study. Hypertension (69.9%) and diabetes mellitus (45.2%) were the most common risk factors among the patients. Thirty nine (21%) of the stroke patients died in hospital. Multiple logistic regression analysis indicated that chronic kidney disease (P = 0.004), number of post-stroke complications (P= 0.037), and stroke subtype (P = 0.015) were independent predictors of in-hospital mortality among the total stroke patients. Knowledge of in-hospital mortality predictors is required to improve survival rate after acute stroke. The study showed that gender was not an independent predictor of mortality after acute stroke. More research is required to understand gender differences in stroke mortality.