Background:We previously developed a non-invasive approach to localize the site of early left ventricular activation origin in real time using 12-lead ECG, and to project the predicted site onto a generic LV endocardial surface using the smallest angle between two vectors algorithm (SA).Objectives:To improve the localization accuracy of the non-invasive approach by utilizing the K-nearest neighbors algorithm (KNN) to reduce projection errors.Methods:Two datasets were used. Dataset #1 had 1012 LV endocardial pacing sites with known coordinates on the generic LV surface and corresponding ECGs, while dataset #2 included 25 clinically-identified VT exit sites and corresponding ECGs. The non-invasive approach used “population” regression coefficients to predict the target coordinates of a pacing site or VT exit site from the initial 120-m QRS integrals of the pacing site/VT ECG. The predicted site coordinates were then projected onto the generic LV surface using either the KNN or SA projection algorithm.Results:The non-invasive approach using the KNN had a significantly lower mean localization error than the SA in both dataset #1 (9.4 vs. 12.5 mm,p< 0.05) and dataset #2 (7.2 vs. 9.5 mm,p< 0.05). The bootstrap method with 1,000 trials confirmed that using KNN had significantly higher predictive accuracy than using the SA in the bootstrap assessment with the left-out sample (p< 0.05).Conclusion:The KNN significantly reduces the projection error and improves the localization accuracy of the non-invasive approach, which shows promise as a tool to identify the site of origin of ventricular arrhythmia in non-invasive clinical modalities.