INTRODUCTION: In patients with acute spinal cord injury (SCI) and degenerative cervical myelopathy (DCM), spinal cord compression is considered a main contributor to spinal cord damage, associated with cerebrospinal fluid (CSF) space obstruction. CSF pressure (CSFP) dynamics are studied as a potential indirect biomechanical marker for spinal cord compression, and as a proxy to estimate spinal cord perfusion pressure (SCPP). RESEARCH QUESTION: Evidence for safety and feasibility of CSFP dynamics in clinical trials as well as interrelations with neuroimaging and intraspinal pressure, and relation to preclinical CSFP models. MATERIAL AND METHODS: Systematic review. This review followed PRISMA guidelines, risk of bias assessment with ROBINS-I tool, PROSPERO registration (CRD42024545629). RESULTS: 11 relevant papers were identified (n = 212 patients, n = 194 intraoperative, n = 18 bedside). Risk of bias for safety reporting was low-moderate. Intraoperative CSFP assessments were commonly performed in acute SCI. CSFP was assessed to calculate SCPP (7/11), to evaluate effects from surgical decompression (5/11) and for therapeutic CSF drainage (3/11). The adverse event rate associated with the intrathecal catheter was 8% (n = 15/194). DISCUSSION AND CONCLUSION: The preliminary safety and feasibility profile of CSFP assessments in spinal cord compression encourages clinical application. However, a deeper risk-benefit analysis is limited as the clinical value is not yet determined, given challenges of defining disease specific critical CSFP and SCPP thresholds. The interrelation between measures of CSFP and neuroimaging is yet to be proven. Targeted preclinical studies are essential to improve our understanding of complex CSFP-cord compression interrelations.