Background: It is not clear whether there is a large difference in acute hemodynamic response (AHR) to left ventricle (LV) pacing in different regions of the same coronary sinus (CS) vein. Using the four electrodes available on a Quartet LV lead, we evaluated the AHR to pacing within individual branches of the CS. Methods: An acute hemodynamic study was attempted in 20 patients. In each patient, we assessed AHR in a number of CS veins and along a significant proportion of each CS branch using three different bipolar configurations. We compared the AHR achieved when pacing using each different vector and also the highest AHR achieved in any position within the same patient with the lowest achieved in that patient. Results: Sixty-four different CS positions in 19 patients were successfully assessed. No significant difference in AHR was found overall between the three vectors tested. The mean percentage difference in AHR between the CS branch vectors with the lowest and highest dP/dt(max) was +6.5 ± 5.4% (P < 0.001). A much larger difference of +16.9 ± 6.1% (P < 0.001) was seen when comparing the highest and lowest AHR achieved using any vector in any position within the same patient. Conclusion: A small difference in AHR is seen when pacing within the same branch of the CS compared to pacing in different branches in the same patient. This suggests that although the site of LV lead placement is important, the position within a CS branch is less important than choosing the right vein.