Background: Drug-induced QT prolongation is a potentially preventable cause of morbidity and mortality, however there are no widespread clinical tools utilized to predict which individuals are at greatest risk. Machine learning (ML) algorithms may provide a method for identifying these individuals, and could be automated to directly alert providers in real time. Objective: This study applies ML techniques to electronic health record (EHR) data to identify an integrated risk-prediction model that can be deployed to predict risk of drug-induced QT prolongation. Methods: We examined harmonized data from the UCHealth EHR and identified inpatients who had received a medication known to prolong the QT interval. Using a binary outcome of the development of a QTc interval >500 ms within 24 hours of medication initiation or no ECG with a QTc interval >500 ms, we compared multiple machine learning methods by classification accuracy and performed calibration and rescaling of the final model. Results: We identified 35,639 inpatients who received a known QT-prolonging medication and an ECG performed within 24 hours of administration. Of those, 4,558 patients developed a QTc > 500 ms and 31,081 patients did not. A deep neural network with random oversampling of controls was found to provide superior classification accuracy (F1 score 0.404; AUC 0.71) for the development of a long QT interval compared with other methods. The optimal cutpoint for prediction was determined and was reasonably accurate (sensitivity 71%; specificity 73%). Conclusions: We found that deep neural networks applied to EHR data provide reasonable prediction of which individuals are most susceptible to drug-induced QT prolongation. Future studies are needed to validate this model in novel EHRs and within the physician order entry system to assess the ability to improve patient safety.