Background: Variations in measured pacing impedances that occur at the time of lead implantation remain largely unexplained and may be due to the morphology of the tissue-lead interface. Methods: An endocardial pacing lead was implanted under direct endoscopic visualization and parameters were measured for defined stages of implantation into multiple sites within the right atrium of in vitro swine hearts (n = 6, 38 implants), in vivo swine hearts (n = 2, 10 implants), and an in vitro human heart (n = 1, 15 implants). Results: Steady increases in impedance values up to 2 turns fully fixed (2TF) were associated with minimal tissue distortion in all implants. Overtorquing of the in vitro swine implants resulted in severe distortion at the tissue-lead interface demonstrating either tissue wrapping (24 implants) or tissue coring (14 implants). Impedance and threshold values remained elevated (953 ± 282 Ω, 7.86 ± 3.0 V; both P < 0.05 vs 2TF) during tissue distortion/wrapping, while tissue-cored implants were associated with significant decreases (552 ± 187 Ω, 6.2 ± 2.2 V; both P < 0.05 vs 2TF). P-wave amplitudes demonstrated no significant changes or correlation to tissue distortion. Importantly, both swine in vivo and human in vitro data demonstrated similar trends compared with the swine in vitro data. Conclusions: In this study, one is able to directly observe and correlate the degree of distortion at the tissue-lead interface with measured electrical parameters. Instantaneous impedance values obtained during fixation serve as a superior indicator of an acceptable lead implantation, and should therefore be carefully monitored during implantation.