Surgical treatment of L5-S1 isthmic spondylolisthesis consists of a combination of decompression and fusion. One previously discussed mode of fusion is via transdiscal screws. Biomechanical studies of transdiscal screws have demonstrated greater rigidity than traditional pedicle screw fixation, which theoretically translates to a higher fusion rate. Furthermore, when compared to pedicle screw fixation, transdiscal screw fixation also demonstrates improved functional and radiographic outcomes. However, transdiscal screw placement can be technically difficult. At this time, a detailed surgical technique has yet to be reported in the literature. Our surgical technique for transdiscal screw placement using intraoperative C-arm at L5-S1 is described. We include considerations for preoperative planning including necessary imaging and appropriate patient selection. We also discuss intraoperative concerns such as setup, surgical approach, proper screw trajectory, and our method for achieving indirect decompression. The results of thirteen consecutive patients treated with transdiscal screw fixation are described. One patient had subcutaneous seroma requiring reoperation (7.7%), three patients had implant failure (23.1%), and one patient had nonunion (7.7%). Our results suggest that transdiscal screw fixation is a safe and acceptable alternative for stabilization and indirect decompression of L5-S1 isthmic spondylolisthesis. Recent innovation in intraoperative navigation and robotic surgery may lessen the technical difficulty of transdiscal screw placement and make it even more effective.