Abstract: Background: The anatomy of the coronary venous system has important implications for clinical interventions including cardiac resynchronization therapy, ablation therapy, defibrillation, perfusion therapy, and mitral valve annuloplasty. Method: The effect of coronary venous anatomy on cardiac therapies was assessed by characterizing the venous anatomy, the clinically relevant adjacent anatomy, and the anatomical effect on pacing thresholds. Coronary venous anatomy was evaluated using perfusion-fixed human cardiac specimens with direct measurements using a microscribe digitizer and with contrast-computed tomography. Contrast-computed tomography and magnetic resonance imaging were used to investigate the coronary venous anatomical relationship with the phrenic nerve, coronary arteries, and mitral isthmus. Finally, electrostatic field simulations were performed to evaluate how cardiac anatomy and pacing electrode location affect clinical pacing thresholds and phrenic nerve stimulation. Results/Discussion: In short, the human coronary venous system is a highly variable physiological system that is essential for several current cardiac therapies. The consistent observation of high anatomical variation throughout all of the performed studies stress the clinical importance of understanding a given patient's individual anatomy when performing a planned intervention within the coronary veins. Importantly, the database of coronary venous anatomical parameters and pacing thresholds presented here can be incorporated into the development and implementation of therapies that utilize these vessels.