Background: Peripherally inserted central catheter tip placement at the cavoatrial junction is associated with reduced catheter-related deep vein thrombosis . Electrocardiographic tip confirmation purportedly improves accuracy of tip placement, but whether this approach can reduce deep vein thrombosis is unknown. Methods: Prospectively collected data from patients that received peripherally inserted central catheters at 52 Michigan hospitals were analyzed. The method used to confirm tip confirmation at insertion and deep vein thrombosis outcomes were extracted from medical records. Multivariate models (accounting for the clustered nature of the data) were fitted to assess the association between peripherally inserted central catheter-related deep vein thrombosis and method of tip confirmation (Electrocardiographic vs. radiographic imaging). Results: A total of 42,687 peripherally inserted central catheters (21,098 radiology vs. 21,589 Electrocardiographic) were included. Patients receiving Electrocardiographic -confirmed peripherally inserted central catheters had fewer comorbidities compared to those that underwent placement via radiology. Overall, deep vein thrombosis occurred in 594 (1.3%) of all peripherally inserted central catheters. Larger catheter size (odds radio [OR]=1.32 [95% confidence interval [CI] 0.93-1.90] per unit increase in gauge), history of deep vein thrombosis, and cancer were associated with increased risk of deep vein thrombosis (OR=2.00 [95%CI 1.65-2.43] and OR=1.62 [95%CI 1.16-2.26], respectively) using logistic regression. Following adjustment, electrocardiographic guidance was associated with a significant reduction in peripherally inserted central catheter-related deep vein thrombosis compared with radiographic imaging (OR=0.74, 95% [CI=0.58-0.93, p=0.0098]). Conclusion: The use of electrocardiographic to confirm peripherally inserted central catheter tip placement at the cavoatrial junction was associated with significantly fewer deep vein thrombosis events than radiographic imaging. Use of this approach for peripherally inserted central catheter insertion may help improve patient safety, particularly in high risk patients.