Objective: Disability and mortality represent the most relevant clinical outcome after acute ischemic stroke. However, validated and comprehensive prognostic models for recovery have not been developed. An accurate model including all previously suggested independent outcome predictors could improve the design and analysis of clinical trials. We therefore developed prognostic models for functional dependence and death after 100 days in a large cohort of stroke patients. Methods: From the German Stroke Database, 1754 prospectively collected records of patients with acute ischemic stroke were used for the development of prognostic models. Intubated patients and patients with low functional status before stroke were excluded. Functional independence was defined as a Barthel Index≥95 after 100 days. Prognostic factors assessable within 72 hours after admission were identified by a systematic literature review. The final models of binary logistic regression analyses were internally validated and calibrated. Results: The resulting cross-validated and calibrated models correctly classified more than 80% of the patients and yielded the following prognostic factors for functional independence: Age, right and left arm paresis at admission, NIH-Stroke Scale at admission, Rankin Scale 48-72 hours later, gender, prior stroke, diabetes, fever, lenticulostriate infarction, neurological complications. The following variables were identified as prognostic factors for death: Age, NIH-Stroke Scale at admission, and fever. Conclusions: Our work gives an important insight into prognostic factors after acute ischemic stroke and presents predictive models with high prognostic accuracy. Together with a prospective validation study, currently underway, we hence hope to improve the prediction of functional outcome after ischemic stroke.