Background: Repetitive transcranial magnetic stimulation (rTMS) and cervical vagus nerve stimulation (VNS) are both FDA approved for the treatment of major depression, while transauricular VNS (taVNS) remains an experimental treatment for depression. VNS stimulates the temporary release of neurotransmitters that promote plasticity, such as acetylcholine and norepinephrine, across the cortex. Theoretically, synchronizing rTMS with VNS could enhance neuroplasticity, potentially providing an additive effect in the treatment of depression. Methods: Our goal is to determine the safety and efficacy of simultaneous VNS and rTMS treatment in patients with treatment-resistant depression. 24 participants with treatment-resistant depression will receive 12 sessions of VNS and sham theta burst rTMS, 12 sessions of unsynchronized VNS and theta burst rTMS (600 pulses per session at 90% resting motor threshold), and 12 sessions of synchronized VNS and rTMS (600 pulses per session at 90% resting motor threshold) in a randomized order. Subjects receive VNS cutaneously through transauricular stimulation if they are new to VNS, or through cervically implanted VNS devices in those who already have a device. Patient Health Questionnaire-9 (PHQ-9 and Hamilton Depression Rating Scale (HDRS) scores are gathered before, during, and up to one month after the trial. Conclusion: To date 4 participants with moderate to severe treatment resistant depression have completed the study. Preliminary findings suggest that combining the two methods is safe and feasible, and 12 sessions of synchronized VNS and rTMS are more effective at acutely reducing depressive symptoms.