Patients with spinal cord injury (SCI) are at high risk of venous thromboembolism (VTE). Pharmacologic VTE prophylaxis (VTEppx) is frequently delayed in patients with SCI because of concerns for bleeding risk. Here, we hypothesized that delaying VTEppx until >48 hours would be associated with increased risk of thrombotic events. This is a secondary analysis of the 2018 to 2020 prospective, observational, cohort Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study of patients aged 18 to 40 years, at 17 US level 1 trauma centers. Patients admitted for >48 hours with documented SCI were evaluated. Timing of initiation of VTEppx, rates of thrombotic events (deep vein thrombosis DVT and pulmonary embolism PE), and missed VTEppx doses were analyzed. The primary outcome was VTE (DVT + PE). There were 343 patients with SCI. The mean ± SD age was 29.0 ± 6.6 years, 77.3% were male, and 78.7% sustained blunt mechanism. Thrombotic events occurred in 33 patients (9.6%): 30 DVTs (8.7%) and 3 PEs (0.9%). Venous thromboembolism prophylaxis started at ≤24 hours in 21.3% of patients and 49.3% at ≤48 hours. The rate of VTE for patients started on VTEppx ≤48 hours was 7.1% versus 12.1% if started after 48 hours ( p = 0.119). After adjusting for differences in risk factors between cohorts, starting ≤48 hours was independently associated with fewer VTEs (odds ratio, 0.45; 95% confidence interval, 0.101-0.978; p = 0.044). Unfractionated heparin was associated with a VTE rate of 21.0% versus 7.5% in those receiving enoxaparin as prophylaxis ( p = 0.003). Missed doses of VTEppx were common (29.7%) and associated with increased thrombotic events, although this was not significant on multivariate analysis. Rates of thrombotic events in patients with SCI are high. Prompt initiation of VTEppx with enoxaparin and efforts aimed at avoiding missed doses are critical to limit thrombotic events in these high-risk patients. Prognostic and Epidemiological; Level IV.