Heterotopic Ossification (HO) refers to the formation of bone within soft tissue. Traumatic spinal cord injury (SCI) has been shown to be associated with development of HO. However, risk factors for HO following SCI are unknown. In light of this knowledge gap, we performed a systematic review and meta-analysis to summarize available evidence and elucidate risk factors associated with heterotopic ossification. An electronic literature search was conducted using five databases. Studies containing SCI patients, with a proportion diagnosed with HO, were included. Meta-analyses were performed to assess the association between following risk factors and development of HO: sex, type of injury, spasticity, pressure ulcer, injury level, urinary tract infection (UTI), deep vein thrombosis (DVT), number of smokers, and pneumonia. Nine studies with 2,115 patients were included. It was found that males (Odds Ratio [95% Confidence Interval]: 2.25 [1.61, 3.13]), smokers (2.88 [1.62, 5.11]), patients with complete injury (3.61 [2.29, 5.71]), pneumonia (2.86 [2.18, 3.75]), pressure ulcers (2.45 [1.89, 3.18]), UTI (3.84 [2.63, 5.62]) and spasticity (2.12 [1.67, 2.68]) had significantly higher odds of developing HO after spinal cord injury. In contrast, location of injury (Cervical vs. thoracic injury; (1.03 [0.72, 1.49]) and DVT (1.37 [0.91, 2.07]) were not associated with development of HO. Pooled results from existing literature on HO development show that several factors are significantly associated with development of HO. Given the complexity of SCI management, the results might have a positive impact on the clinical practice by leading to an effective screening aproach.Copyright © 2020 Elsevier B.V. All rights reserved.