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Immunomodulatory therapeutics represent a potential neuroprotective strategy for the management of acute spinal cord injury (SCI). One of the most intensely debated neuroprotective drugs has been methylprednisolone sodium succinate (MPSS). MPSS was initially investigated for its role in mitigating lipid peroxidation. More recently, the anti-inflammatory/immunomodulatory properties of MPSS have been increasingly appreciated. Over the past two decades, several systematic reviews and clinical practice guidelines related to MPSS use in SCI have been published. The goal of this study was to investigate the temporal changes in the use of steroids at North American Clinical Trials Network (NACTN) centers and to correlate these with the evolution in published literature and guidelines. Data on patients enrolled from 2008 - 2018 in the prospective, multicenter NACTN registry, and in whom information related to the use of steroids was available, were analyzed. Patients were stratified as to whether they received steroids or not. The primary outcome was the change in the rate of steroid use per year between 2008 and 2018. Secondary outcomes included cardiac, gastrointestinal & genitourinary (GIGU), pulmonary and dermatologic complications. We identified 608 patients, of whom 171 (28.1%) were given steroids. In 2008 and 2009, the prevailing paradigm across NACTN centers was in favor of steroid administration and as such 70% (n=56) of patients received steroids in 2008 and 71.9% (n=46) in 2009. An abrupt practice reversal was observed in 2010, whereby only 19.7% of patients (n=14) received steroids, a trend that continued over subsequent years. Increasing literature in the 2000s arguing against the use of steroids culminated in the 2013 CNS/AANS practice guidelines for the management of acute SCI. These guidelines recommended against the use of MPSS for the treatment of acute SCI. Over the following years (2013-2018), steroids continued to be an uncommonly used therapeutic option in NACTN centers (range 3.9-16.9%). Patients receiving steroids had significantly higher rates of pulmonary complications (87%, n=147) compared to those not receiving steroids (73%, n=265; p=0.0003). However, compared to patients receiving steroids, those who did not receive steroids had significantly higher rates of cardiac (40%, [n=146] versus 23%, [n=39]; p=0.0001) and gastrointestinal/genitourinary complications (55%, [n=189], versus 31%, [n=52]; p<0.0001). The 2013 AANS/CNS guidelines and preceding literature appeared to have an impact on dramatically lowering the rates of corticosteroid use for acute SCI in NACTN sites after 2009. Of note, this analysis may not reflect the impact of the 2017 AO Spine Clinical Practice guidelines, which suggested the use of methylprednisolone as a valid practice option for acute SCI, especially for cervical injuries. Enhanced patient involvement in the clinical decision-making process and opportunities to personalize SCI management exist in reference to the use of MPSS in acute SCI.