Purpose <p>The treatment of vertebral osteomyelitis (VO) is multifaceted. In most cases, patients are treated conservatively. In the past, it has already been shown that the quality of life is improved by surgery compared to conservative treatment. Recently it was also shown that surgical treatment of VO improves recurrence and mortality. Indications of a surgical approach can be relative or absolute. Absolute indications include, above all, severe bony destruction. The aim of this study is to identify risk factors for severe destruction in comparison to minor to or not to moderate destruction.</p> Methods <p>This monocentric study included 355 patients with VO from the DWG- and the former European Spine Tango-Registry. The primary aim was to analyze the risk factors for severe destruction, the secondary aim was to determine the outcomes between the different degrees of severity.</p> Results <p>The prediction model for severe destruction with the factors age ≥ 65 years, gender, CRP ≥ 10&#xa0;mg/L, an ASA class above two, a BMI ≥ 25&#xa0;kg/m², a bacteremia, more than two comorbidities, more than one segment affected, detected pathogen, Staphylococcus aureus as pathogen, a previous injection or surgery was significant as a whole (Chi²(12) = 22.48, <i>p</i> = 0.032, <i>n</i> = 355). An ASA class of three and higher increased the risk of severe destruction by 1.77 times (<i>p</i> = 0.027), a BMI ≥ 25&#xa0;kg/m² reduced the risk by 0.6 times (<i>p</i> = 0.03) and a previous surgery reduced the risk by 0.5 times (<i>p</i> = 0.04). Survival was longer for mild to moderate destruction compared to severe destruction 142 (95%CI 125–142) days vs. 72 (95%CI 47–99) days (<i>p</i> = 0.001).</p> Conclusions <p>Multimorbid patients with native VO exhibit more severe bony destruction. These patients are high-risk VO patients with an increased 1-year mortality rate. Therefore an early indication for surgical treatment may proof advantageous.</p>