Objectives: Pyogenic vertebral osteomyelitis (PVO) is associated with a high burden of disease. Our study aimed to describe characteristics at presentation of PVO, the risk of inadequate treatment response (ITR), relapse, and death, and to determine risk factors for ITR. Methods: Patients with an ICD-10 discharge code for PVO and admission to a major Danish university hospital between November 2016 and April 2019 were included. ITR was defined as clinical, microbiological, and/or radiological progression during treatment. Data were collected through review of medical records, and logistic regression was used to determine adjusted odds ratios (aOR). Results: Of 106 patients included, 87% presented with pain in the spine, 97% elevated CRP, 14% severe sepsis, and 13% with a history of previous spinal surgery. 39% were infected with Staphylococcus aureus and 9% with Escherichia coli. 31% responded inadequately to treatment, and risk factors for ITR were previous spinal surgery (aOR 19.29; 95% confidence interval (CI) 2.20–169.08), severe sepsis (aOR 4.59; 95% CI 1.28–15.41), and infection with Escherichia coli (aOR 8.10; 95% CI 1.71–38.45). 13% experienced relapse within the first 2 years, while the 1-year crude mortality was 12%. Conclusion: Staphylococcus aureus is still the main pathogen in PVO patients, and the risks of relapse and mortality remain high. Factors found to be associated with ITR were previous spinal surgery, severe sepsis, and infection with Escherichia coli.