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Introduction: The SEDAN-S score was developed in a rural setting and showed high accuracy predicting hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolytics. It encompasses clinical, laboratory, and radiographic parameters. We aimed to externally validate the score in an urban population. Methods: We reviewed patients with acute ischemic stroke treated with intravenous thrombolytics at a Large Urban Academic Hospital with Comprehensive Stroke Center designation from January 2022 to October 2024. Demographics, clinical presentations, laboratory values, and neuroimaging were collected. HT present in neuroimaging within 24 hours after rtPA was recorded, and the subgroup of symptomatic intracerebral hemorrhage (sICH) was noted. The cohort was divided into two groups, HT and NoHT. The two groups were compared by univariate analyses. Propensity-score matching (PSM) was applied to balance demographics and comorbidities between the two groups. Length of stay, mortality, and 30-day mRS were analyzed between the two matched groups. SEDAN and SEDAN-S scores were calculated, and the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval was computed for each model. P value was set at 0.05. Results: Among 200 patients included in this study a total of 22 (11%) developed HT. The two groups were comparable in demographics and baseline comorbidities. HT group had higher median NIHSS (17 [10-18] vs. 10 [5-15], p<0.01), lower median ASPECT score (7 [6-9] vs. 9 [7-10], p<0.01) and higher rate of large vessel occlusion (68.2% vs. 45.5% p=0.045), compared to NoHT group. SEDAN score demonstrated significantly higher accuracy in predicting HT after rtPA (AUC=0.65, 95%CI:0.54-0.76) compared to SEDAN-S score (AUC=0.61, 95%CI:0.49-0.72), p=0.034. After PSM 1:1, only the subgroup of sICH remained independently associated with in-hospital mortality (OR: 8, 95%CI: 1.87-73.55, p=0.03) and lower odds of mRS 0-2 at 30 days (OR:0.19, 95%CI: 0.065-0.555, p=0.002). Conclusions: In the urban setting, SEDAN score retains a better accuracy in predicting HT after thrombolytics compared to SEDAN-S score, highlighting inherent differences between urban and rural populations. Among HT, only the subgroup of sICH is associated with higher odds of in-hospital mortality and lower likelihood of favorable short-term outcome.