Background: Despite declining age-adjusted stroke mortality rates, the disease remains the third most common cause of death in Israel. Based on a national survey, we examined mortality rates during the first 3 years after a first-ever acute ischemic stroke (IS) and the major predictors of short-term (1 month) and long-term (3 years) mortality. Methods: In the National Acute Stroke Israeli Survey (NASIS 2004), data were collected on all hospitalized stroke patients in Israel during a 2-month period. Mortality rates for first-ever IS were assessed at 1 month and 3 years and predictors of death were evaluated using the Cox proportional hazard model. Results: A total of 1,079 first-ever IS patients were included. Survival data were complete for over 99% of patients. Cumulative mortality rates were 9.9% at 1 month and 31.1% at 3 years. Of the survivors at 1 month, 23.5% did not survive for 3 years. At 1 month, the hazard ratio (HR) for death significantly increased with stroke severity. One-month mortality was also associated with a decreased level of consciousness (HR 2.9, 95% CI 1.7–5.1), total anterior circulation infarction (TACI); HR 4.9, 95% CI 1.6–15.2), temperature on admission (HR 1.5, 95% CI 1.1–2.1 per 1°C), age (HR 1.04, 95% CI 1.02–1.07 per year) and glucose levels on admission (HR 1.003, 95% CI 1.001–1.006 per 1 mg/dl). Age-adjusted proportions of diabetes and chronic heart failure were considerably higher in the deceased compared with survivors at 3 years (48 vs. 38 and 21 vs. 9%, respectively). In the multivariate survival analyses, predictors of death at 1 month also predicted death at 3 years; however, history of dementia (HR 1.5, 95% CI 1.0–2.4), diabetes (HR 1.6, 95% CI 1.0–2.4), peripheral artery disease (HR 1.7, 95% CI 1.1–2.8), chronic heart failure (HR 1.6, 95% CI 1.1–2.4) and malignancy (HR 1.7, 95% CI 1.1–2.7) were additional predictors of long-term mortality for patients surviving the first month after stroke. Conclusions: Approximately one third of patients did not survive 3 years after the first-ever IS. While age and markers of severe stroke were the major predictors of death at 1 month, comorbidities and variables associated with atherosclerotic vascular disease predicted long-term mortality. Improved control of these factors can potentially reduce long-term mortality in stroke victims.