OBJECTIVE The intramedullary route holds the potential to provide the most concentration of stem cells in cases of spinal cord injury (SCI). However, the safety and feasibility of this route need to be studied in human subjects. The aim of this study was to evaluate the safety and feasibility of intramedullary injected bone marrow–derived mesenchymal stem cells (BM-MSCs) in acute complete SCI. METHODS In this prospective study conducted over a 2-year period, 27 patients with acute (defined as within 1 week of injury) and complete SCI were randomized to receive BM-MSC or placebo through an intramedullary route intraoperatively at the time of spinal decompression and fusion. Institutional ethics approval was obtained, and informed consent was obtained from all patients. Safety was assessed using laboratory and clinicoradiological parameters preoperatively and 3 and 6 months after surgery. RESULTS A total of 180 patients were screened during the study period. Of these, 27 were enrolled in the study. Three patients withdrew, 3 patients were lost to follow-up, and 8 patients died, leaving a total of 13 patients for final analysis. Seven of these patients were in the stem cell group, and 6 were in the control group. Both groups were well matched in terms of sex, age, and weight. No adverse events related to stem cell injection were noted for laboratory and radiological parameters. Five patients in the control group and 3 patients in the stem cell group died during the follow-up period. CONCLUSIONS Intramedullary injection of BM-MSCs was found to be safe and feasible for use in patients with acute complete SCI.