Various surgical procedures may cause temporary interruption of spinal cord blood supply and may result in irreversible ischemic injury and neurological deficits. The cascade of events that leads to neuronal death following ischemia may be amenable to pharmacological manipulations that aim to increase the tolerable duration of ischemia. Many agents have been evaluated in experimental spinal cord ischemia (SCI). In order to investigate whether an agent is available that justifies clinical evaluation, the literature on pharmacological neuroprotection in experimental SCI was systematically reviewed to assess the neuroprotective efficacy of the various agents. In addition, the strength of the evidence for neuroprotection was investigated by analyzing the methodology. The authors used a systematic review to conduct this evaluation. The included studies were analyzed for neuroprotection and methodology. In order to be able to compare the various agents for neuroprotective efficacy, relative risks and confidence intervals were calculated from the data in the results sections. A total of 103 studies were included. Seventy-nine different agents were tested. Only 14 of the agents tested did not afford protection at all. A large variation was observed in the experimental models to produce SCI. This variation limited comparison of the individual agents. In 48 studies involving 31 single agents, the relative risks and confidence intervals could be calculated. An analysis of the methodology revealed poor temperature management and lack of statistical power in the majority of the 103 studies. The results suggest that numerous agents may protect the spinal cord from transient ischemia. However, poor temperature management and lack of statistical power severely weakened the evidence. Consequently, clinical evaluation of pharmacological neuroprotection in surgical procedures that carry a risk of ischemic spinal cord damage is not justified on the basis of this study.