BACKGROUND The aim of this study was to explore the relationship between the α2-HS glycoprotein concentrations in serum and the occurrence of neurogenic heterotopic ossification (NHO) in patients with spinal cord injury (SCI). MATERIAL AND METHODS During the period between January 2011 and January 2012, 75 patients (67 male) with paraplegia caused by spinal cord injury were enrolled. The patients were divided into 2 groups in accordance with the occurrence of heterotopic ossification based on the results high-frequency ultrasound on the bilateral hip joint. The levels of α2-HS glycoprotein, C-reactive protein (CRP), D-dimer, and bone morphogenetic protein (BMP) were detected by ELISA. RESULTS We found a significant decrease of α2-HS glycoprotein in SCI patients with NHO compared to SCI patients without NHO. In contrast, a significant elevation of serum calcium, D-dimer, BMP, and CRP was observed in SCI patients with NHO. The degree of maturity of NHO did not influence the level of α2-HS glycoprotein. Multivariate liner regression analysis showed that the level of serum α2-HS glycoprotein was correlated with CRP and spasticity. CONCLUSIONS The decreased level of α2-HS glycoprotein may be related to the formation of neurogenic heterotopic ossification in patients with spinal cord injury. Our results suggest that α2-HS glycoprotein might be a risk factor for NHO in patients with SCI.