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Background: Risks of neurological deterioration after heparin administration following cervical spinal cord injury (SCI) in humans are unknown., Objective: To elucidate the safety of heparin following cervical SCI and investigate its potential neuroprotectant role., Methods: Sixty-two Sprague Dawley adult rats were subjected to mild (0.6 mm), moderate (0.9 mm), or severe (1.2 mm) C7-SCI. At each injury severity, intravenous heparin or saline was administered for 72 hours following SCI. Behavioral tests (Basso, Beattie, Bresnahan scores, Hargreave's) were performed before killing the rats at week 7. Half of the rats were killed at day 3, and the remainder at week 7 after SCI. Immunohistochemistry, Western blot analysis, and axonal retrograde tracing were conducted at both times., Results: Subpial hemorrhage was greater in heparin-treated animals compared with controls at all severities of SCI day 3 after injury. Counterintuitively, intraparencyhmal hemorrhage was minimal in the lesion epicenter following mild SCI in the heparin-treated animals compared with controls. India ink perfusion revealed greater preservation of microcirculation in heparin-treated animals compared with a reduction in control animals. A decrease in spinal cord perfusion correlated directly with an increase in hypoxia-inducible factor-1α expression. There was significant gray matter sparing, but no change in white matter volume after heparin treatment at week 7 in the mild SCI group. Beneficial effects on hemorrhagic volume, axon sparing, and functional recovery following heparin treatment were not observed in the moderate or severe SCI group., Conclusion: Heparin treatment following SCI is safe at all degrees of injury. Heparin decreases platelet aggregation and microvascular occlusion, providing a potential neuroprotective effect following mild SCI.