Background and Purpose-Pretreatment lesion size on diffusion-weighted imaging (DWI) is a risk factor for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment. Here, we investigated whether the Alberta Stroke Programme Early CT Score (ASPECTS) applied to DWI images (DWI-ASPECTS) predicts sICH risk accurately. Methods-In this retrospective multicenter study, prospectively collected data of 217 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours after symptom onset were analyzed. Pretreatment DWI-ASPECTS scores were assessed by 2 independent investigators. For bleeding risk analysis, DWI-ASPECTS scores were either categorized into 0 to 7 (n = 105) or 8 to 10 (n = 112) or in 3 groups of similar sample size (DWI-ASPECTS 0 to 5 [n = 69], 6 to 7 [n = 70], and 8 to 10 [n = 78]). Results-DWI-ASPECTS scores correlated well with the DWI lesion volume (r = 0.77, P < 0.001, Spearman Rank test). Interobserver reliability for the assessment of DWI-ASPECTS was moderate (weighted kappa 0.441 [95% CI 0.373 to 0.509]). Twenty-three (10.6%) patients developed sICH. The sICH rate was significantly higher in patients with DWI-ASPECTS scores 0 to 7 (n = 21, 15.1%) as compared to patients with DWI-ASPECTS scores 8 to 10 (n = 2, 2.6%, P = 0.004). sICH risk was 20.3%, 10%, and 2.6% in the 0 to 5, 6 to 7, and 8 to 10 DWI-ASPECTS groups, respectively. DWI-ASPECTS remained an independent prognostic factor for sICH after adjustment for clinical baseline variables (age, NIHSS, time to thrombolysis). Conclusions-DWI-ASPECTS predicts sICH risk after thrombolysis and may be helpful to contributing to quick sICH risk assessment before thrombolytic therapy. (Stroke. 2009; 40: 2743-2748.)