Background: Cell-based therapies are a promising treatment option for traumatic, tumorigenic and degenerative diseases of the spinal cord. Transplantation into the spinal cord is achieved with intravascular, intrathecal, or direct intraparenchymal injection. The current standard for direct injection is limited by surgical invasiveness, difficulty in reinjection, and the inability to directly target anatomical or pathological landmarks. The objective of this study was to present the proof of principle for minimally invasive, percutaneous transplantation of stem cells into the spinal cord parenchyma of live minipigs under MR guidance. Methods: An MR-compatible spine injection platform was developed to work with the ClearPoint SmartFrame system (MRI Interventions Inc.). The system was attached to the spine of 2 live minipigs, a percutaneous injection cannula was advanced into the spinal cord under MR guidance, and cells were delivered to the cord. Results: A graft of 2.5 × 106 human (n = 1) or porcine (n = 1) neural stem cells labeled with ferumoxytol nanoparticles was transplanted into the ventral horn of the spinal cord with MR guidance in 2 animals. Graft delivery was visualized with postprocedure MRI, and characteristic iron precipitates were identified in the spinal cord by Prussian blue histochemistry. Grafted stem cells were observed in the spinal cord of the pig injected with porcine neural stem cells. No postoperative morbidity was observed in either animal. Conclusion: This report supports the proof of principle for transplantation and visualization of pharmacological or biological agents into the spinal cord of a large animal under the guidance of MRI.