Background Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to develop and validate a risk score for QT prolongation in hospitalized patients. Methods and Results In this study, in a single tertiary care institution, consecutive patients (n=900) admitted to cardiac care units comprised the risk score development group. The score was then applied to 300 additional patients in a validation group. Corrected QT (QT(c)) interval prolongation (defined as QT(c)>500 ms or an increase of >60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the development group and validation group, respectively. Independent predictors of QT(c) prolongation included the following: female (odds ratio, 1.5; 95% confidence interval, 1.1-2.0), diagnosis of myocardial infarction (2.4 [1.6-3.9]), septic shock (2.7 [1.5-4.8]), left ventricular dysfunction (2.7 [1.6-5.0]), administration of a QT-prolonging drug (2.8 [2.0-4.0]), 2 QT-prolonging drugs (2.6 [1.9-5.6]), or loop diuretic (1.4 [1.0-2.0]), age >68 years (1.3 [1.0-1.9]), serum K+ <3.5 mEq/L (2.1 [1.5-2.9]), and admitting QT(c) >450 ms (2.3; confidence interval [1.6-3.2]). Risk scores were developed by assigning points based on log odds ratios. Low-, moderate-, and high-risk ranges of 0 to 6, 7 to 10, and 11 to 21 points, respectively, best predicted QT(c) prolongation (C statistic=0.823). A high-risk score 11 was associated with sensitivity=0.74, specificity=0.77, positive predictive value=0.79, and negative predictive value=0.76. In the validation group, the incidences of QT(c) prolongation were 15% (low risk); 37% (moderate risk); and 73% (high risk). Conclusions A risk score using easily obtainable clinical variables predicts patients at highest risk for QT(c) interval prolongation and may be useful in guiding monitoring and treatment decisions.