OBJECTIVE: The purpose of this study was to examine the utility and feasibility of using alternative anterior reference leads when measuring left posterior tibial nerve somatosensory evoked potentials (SEPs). METHODS: With IRB approval, 12 patients were monitored using both traditional (FPz and C4') and alternative anterior (F3 and F4) reference leads during routine spine surgery with SEP monitoring. Recordings from the routine and novel electrode pairs were collected and analyzed. RESULTS: All of the SEP amplitudes measured were of similar magnitude except for that of F3-F4, which was significantly lower (P < 0.001) than all of the other five lead combinations which were assessed (Cz'-FPz, C3'-C4', C3'-F4, Cz'-F3, and Cz'-F4). The latencies of the novel lead combinations (C3'-F4, Cz'-F3, Cz'-F4, and F3-F4) were similar to those of the "gold standards" (Cz'-FPz and C3'-C4') (pooled median, 45.6 ms with 25-75th percentiles, 44.0-47.8 ms, P = 0.308). The coefficients of variation (CV %) of the amplitudes were not statistically significantly different (P = 0.341). CONCLUSIONS: The use of alternative frontal reference leads (F3 and F4) for left posterior tibial nerve SEP monitoring yields signals of equal quality and reproducibility compared to signals with standard (FPz and C4') referencing. These alternative leads may substitute for traditional referencing when placement of FPz or C4' is precluded by the location of surgery.