Background: Endocardial lead in the right ventricle is recognized as a cause for tricuspid regurgitation (TR), but the mechanism remains elusive. We sought to evaluate lead-specific features on the development of TR after endocardial lead implantation. Methods: This was a prospective single-center study. The patients underwent 2-dimensional echocardiograms before endocardial lead implantation and at follow-up visits at 4 to 6 weeks, 6 months, and 12 months. We assessed the position of the endocardial lead at the tricuspid annulus by 3-dimensional echocardiography, the tricuspid leaflet interference by the endocardial lead by both 2- and 3-dimensional echocardiography, and the degree of lead slack radiologically. Patient characteristics and lead-related factors were evaluated in the prediction of new or worse TR by univariable and multivariable analyses. Results: New or increased TR was detected in 38 of 128 patients at the 12-month follow-up. The postero-septal commissure was the most common lead position, and tricuspid leaflet interference detected in 21 patients was associated with a noncommissural lead position. The implantation of an implantable cardioverter defibrillator lead was not associated with new TR compared with the implantation of a pacemaker lead. Tricuspid leaflet interference (P < 0.0001), but not lead position or lead slack, was the only lead-specific factor associated with the development of TR. Conclusion: After right ventricle endocardial lead implantation, leaflet interference determined by echocardiography, but not the nature of the lead, the lead position at the tricuspid annulus, and the radiological lead slack, predicted TR development at 1 year postimplantation.