Objective: A study was undertaken to develop a score for assessing risk for symptomatic intracranial hemorrhage (sICH) in ischemic stroke patients treated with intravenous (IV) thrombolysis. Methods: The derivation cohort comprised 974 ischemic stroke patients treated (1995–2008) with IV thrombolysis at the Helsinki University Central Hospital. The predictive value of parameters associated with sICH (European Cooperative Acute Stroke Study II) was evaluated, and we developed our score according to the magnitude of logistic regression coefficients. We calculated absolute risks and likelihood ratios of sICH per increasing score points. The score was validated in 828 patients from 3 Swiss cohorts (Lausanne, Basel, and Geneva). Performance of the score was tested with area under a receiver operating characteristic curve (AUC‐ROC). Results: Our SEDAN score (0 to 6 points) comprises baseline blood Sugar (glucose; 8.1–12.0mmol/l 145–216mg/dl = 1; >12.0mmol/l >216 mg/dl = 2), Early infarct signs (yes = 1) and (hyper)Dense cerebral artery sign (yes = 1) on admission computed tomography scan, Age (>75 years = 1), and NIH Stroke Scale on admission (≥10 = 1). Absolute risk for sICH in the derivation cohort was: 1.4%, 2.9%, 8.5%, 12.2%, 21.7%, and 33.3% for 0, 1, 2, 3, 4, and 5 score points, respectively. In the validation cohort, absolute risks were similar (1.0%, 3.5%, 5.1%, 9.2%, 16.9%, and 27.8%, respectively). AUC‐ROC was 0.77 (0.71–0.83; p < 0.001). Interpretation: Our SEDAN score reliably assessed risk for sICH in IV thrombolysis‐treated patients with anterior‐ and posterior circulation ischemic stroke, and it can support clinical decision making in high‐risk patients. External validation of the score supports its generalization. ANN NEUROL 2012;