The goal of this study was to compare the motor response to sacral neuromodulation (SNM) with different pairs of stimulating electrodes in anesthetized and awake sheep. Similar to SNM clinical use in humans, the InterStim quadripolar tined lead was implanted adjacent to the S3 nerve root in sheep and bipolar stimulation was configured with one electrode negative and one electrode positive on the four contacts (0 most distal to device, 1, 2, and 3 most proximal). Electrode 3-cathode and electrode 0-anode (3-/0+) stimulation had the lowest visual response threshold (0.46 ± 0.14V, anesthetized, 0.56 ± 0.21V, conscious), representing the most sensitive stimulation. Stimulation on electrode 0 (0-/1+) had the highest response threshold among tested electrodes (2.70 ± 0.23V, anesthetized, 3.38 ± 0.96V, conscious). The order according to response threshold from low to high was 3 < 2 < 1 < 0. The triggered response by 3-/0+ stimulation solely occurred in the perineum, tail, or bellows. In contrast, the 0-/1+ stimulation frequently evoked response in gluteal and thigh regions. The electromyographic activities from the anus were sensitive to low intensities of stimulation on electrode 3 (e.g., 3-/0+, 3-/2+). Objective motor responses to SNM as a functional indicator for optimal lead placement may be used to demonstrate that the contact which is most proximal to the foramen (electrode 3) is an optimal electrode to trigger an "on-target" response to lower intensity stimulation. Data from this preclinical work suggest that there are several principles that may be referenced to simplify and expedite the programming process in clinical practice.