QTc prolongation has a high prevalence of and is associated with increased all-cause mortality. Nonetheless, QTc prolonging medications are often used during patient hospitalizations despite baseline prolongation and QTc changes. Data regarding the real-world relative risk of QTc prolongation in the hospital setting are lacking. In this study, we sought to quantify the degree and relative risk of QTc prolongation in patients receiving Arizona Center for Education and Research on Therapeutics (AzCERT) “known risk” medications. Electronic medical records of patients receiving an electrocardiogram at the University of Chicago, admitted in 2011 were analyzed. The longest QTc interval and medications administered within the preceding 24 hours were evaluated. Medications were classified into 4 categories according to the AzCERT classification. Of a total of 14,804 patients, mean QTc intervals were 485 versus 454 ms for men and 469 versus 453 ms for women receiving known risk medications compared with those receiving no risk medications (p <0.001). The rate of QTc prolongation was 71% versus 48% for men and 50% versus 34% for women, respectively. There was no significant increase in QTc prolongation for patients administered multiple QT-relevant medications or for those administered only conditional or possible risk medications. In conclusion, the prevalence of significant QTc prolongation in patients receiving AzCERT known risk medications is high. This may be a reflection of inadequate awareness or overall quality inadequacies.