Background: Intracerebral hemorrhage is a feared complication of IV thrombolytic (rt-PA) therapy. In recent years, at least 8 clinical scores have been proposed to predict either adverse outcome or symptomatic intracerebral hemorrhage (sICH) in patients undergoing rt-PA therapy. The purpose of this study was to evaluate the ability of these 8 scores to predict sICH in an independent clinical dataset. Methods: Clinical data was analyzed from consecutive patients (n = 210) receiving IV rt-PA therapy from January 2009 to December 2013 at Yale-New Haven Hospital. Eight scores were calculated for each patient: Stroke-TPI, DRAGON, SPAN-100, ASTRAL, PRS, HAT, SEDAN, and SITS-ICH. sICH was defined according to the NINDS study criteria. Univariate logistic regression was performed using each score as an independent variable and sICH as the dependent variable. Goodness of fit was tested by Receiver operating characteristic (ROC) analysis and by Hosmer–Lemeshow statistics. Results: sICH occurred in 12 patients (5.71 %) after IV rt-PA treatment. Only 4 scores predicted sICH with good accuracy (ROC area >0.7): DRAGON 0.76 (0.63, 0.89); Stroke-TPI 0.74 (0.61, 0.87); ASTRAL 0.72 (0.59, 0.86); and HAT 0.70 (0.55, 0.85), with odds ratios as follows: Stroke-TPI, 1.91 (1.26, 2.90); HAT, 1.67 (1.06, 2.62); DRAGON, 1.66 (1.21, 2.30); and ASTRAL, 1.10 (1.03, 1.16). Conclusions: Three scores showed good agreement with sICH: DRAGON, Stroke-TPI, and HAT with odds ratios substantially greater than 1. Stroke-TPI and HAT additionally benefited from low computational complexity and therefore performed best overall. Our results demonstrate the utility of clinical scores as predictors of sICH in acute ischemic stroke patients undergoing IV thrombolytic therapy.