Objective: To determine the demographic and clinical predictors of in-hospital mortality among hospitalized nursing home (NH) residents. Design: Retrospective analysis of the public-use copies of the 2005-2006 National Hospital Discharge Survey (NHDS) datasets. Setting: Non-federal acute-care, short-stay hospitals in all 50 states and the District of Columbia. Participants: Participants were 1904 and 1752 NH residents, 45 years or older, hospitalized in 2005 and 2006, respectively. Measurements: In-hospital mortality. Methods: A multivariable logistic regression model was developed to determine independent predictors of in-hospital mortality using the 2005 dataset. The model was then applied to the 2006 dataset to determine the generalizability of the predictors. Results: Significant independent predictors of in-hospital mortality in 2005 included age 85 years or older (adjusted odds ratio [OR], 2.53; 95% confidence interval [CI], 1.21-5.30; P=.013), acute respiratory failure (adjusted OR, 5.67; 95% CI, 3.51-9.17; P < .0001), septicemia (adjusted OR, 4.63; 95% CI, 3.08-6.96; P < .0001), and acute renal failure (adjusted OR, 2.11; 95% CI, 1.30-3.41; P=.002). The following baseline characteristics also predicted in-hospital mortality in 2006: age 85 years or older (adjusted OR, 2.45; 95% CI, 1.31-4.59; P=.005), acute respiratory failure (adjusted OR, 7.11; 95% CI, 4.46-11.33; P < .0001), septicemia (adjusted OR, 3.91; 95% CI, 2.64-5.80; P < .0001), and acute renal failure (adjusted OR, 2.75; 95% CI, 1.82-4.15; P < .0001). Chronic morbidities were not associated with in-hospital mortality. Conclusion: Among hospitalized NH residents, age 85 years or older and several acute conditions, but not chronic morbidities, predicted in-hospital mortality. Elderly NH residents at risk of developing these acute conditions may benefit from palliative care.