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Background The objective of the study was to identify factors predictive of 6-month institutionalization or mortality in frail elderly patients after acute hospitalization. Methods A prospective cohort of elderly subjects 75 years and older was set up in nine French teaching hospitals. Data obtained from a comprehensive geriatric assessment were used in a Cox model to predict 6-month institutionalization or mortality. Institutionalization was defined as incident admission either to a nursing home or other long-term care facility during the follow-up period. Results Crude institutionalization and death rates after 6 months of follow-up were 18% and 24%, respectively. Independent predictors of institutionalization were: living alone (HR = 1.83; 95% CI = 1.27–2.62) or a higher number of children (HR = 0.86; 95% CI = 0.78–0.96), balance problems (HR = 1.72; 95% CI = 1.19–2.47), malnutrition or risk thereof (HR = 1.93; 95% CI = 1.24–3.01), and dementia syndrome (HR = 1.88; 95% CI = 1.32–2.67). Factors found to be independently related to 6-month mortality were exclusively medical factors: malnutrition or risk thereof (HR = 1.92; 95% CI = 1.17–3.16), delirium (HR = 1.80; 95% CI = 1.24–2.62), and a high level of comorbidity (HR = 1.62; 95% CI = 1.09–2.40). Institutionalization (HR = 1.92; 95% CI = 1.37–2.71) and unplanned readmission (HR = 4.47; 95% CI = 3.16–2.71) within the follow-up period were also found as independent predictors. Conclusion The main factors predictive of 6-month outcome identified in this study are modifiable by global and multidisciplinary interventions. Their early identification and management would make it possible to modify frail elderly subjects’ prognosis favorably.