Background: Thoracolumbar spine fractures in multiple-injured patients are a common injury pattern. The appropriate timing for the surgical stabilization of vertebral fractures is still controversial. The purpose of this study was to analyse the impact of the timing of spinal surgery in multiple-injured patients both in general and in respect to spinal injury severity. Methods: A retrospective analysis of multiple-injured patients with an associated spinal trauma within the thoracic or lumbar spine (injury severity score (ISS) >16, age >16 years) was performed from January 2012 to December 2016 in two Level I trauma centres. Demographic data, circumstances of the accident, and ISS, as well as time to spinal surgery were documented. The evaluated outcome parameters were length of stay in the intensive care unit (ICU) (iLOS) and length of stay (LOS) in the hospital, duration of mechanical ventilation, onset of sepsis, and multiple organ dysfunction syndrome (MODS), as well as mortality. Statistical analysis was performed using SPSS. Results: A total of 113 multiple-injured patients with spinal stabilization and a complete dataset were included in the study. Of these, 71 multiple-injured patients (63%) presented with an AOSpine A-type spinal injury, whereas 42 (37%) had an AOSpine B-/C-type spinal injury. Forty-nine multiple-injured patients (43.4%) were surgically treated for their spinal injury within 24 h after trauma, and showed a significantly reduced length of stay in the ICU (7.31 vs. 14.56 days; p < 0.001) and hospital stay (23.85 vs. 33.95 days; p = 0.048), as well as a significantly reduced prevalence of sepsis compared to those surgically treated later than 24 h (3 vs. 7; p = 0.023). These adverse effects were even more pronounced in the case where cutoffs were increased to either 72 h or 96 h. Independent risk factors for a delay in spinal surgery were a higher ISS (p = 0.036), a thoracic spine injury (p = 0.001), an AOSpine A-type spinal injury (p = 0.048), and an intact neurological status (p < 0.001). In multiple-injured patients with AOSpine A-type spinal injuries, an increased time to spinal surgery was only an independent risk factor for an increased LOS; however, in multiple-injured patients with B-/C-type spinal injuries, an increased time to spinal surgery was an independent risk factor for increased iLOS, LOS, and the development of sepsis. Conclusion: Our data support the concept of early spinal stabilization in multiple-injured patients with AOSpine B-/C-type injuries, especially of the thoracic spine. However, in multiple-injured patients with AOSpine A-type injuries, the beneficial impact of early spinal stabilization has been overemphasized in former studies, and the benefit should be weighed out against the risk of patients’ deterioration during early spinal stabilization.