The aim of the study was to assess disease characteristics and outcome in patients with vertebral osteomyelitis (VO). A two medical centre retrospective cohort study was performed by chart review after discharge of 110 patients with confirmed VO treated during a 5-year period. Patients were divided in two groups: patients with uncomplicated VO and patients with complicated VO. All patients underwent clinical and biological examinations and magnetic resonance imaging (MRI) according to the same protocol. Patients with complicated VO were significantly older (p = 0.038). They were longer treated with antibiotics parenterally (p = 0.047) and more often surgically (p < 0.001). In these patients, high Charlson comorbidity index (CCI) score was more often observed (p = 0.024), as well as liver cirrhosis (p = 0.013) and degenerative spine disease (p = 0.007) as comorbidities. Patients with advanced MRI changes of VO had a modified CCI score of 2 or more (p = 0.006). They more often experienced neurological deficit (p = 0.021). Staphylococcus aureus was the most frequently isolated bacterium from blood and tissue samples. Advanced MRI changes and complicated VO were more often observed in patients with high CCI score due to impaired immune system caused by chronic comorbid disease(s) or modulation of immunity with medications. High CCI scores were more frequently associated with positive blood cultures due to bacteremia because of impaired immunity. Patients with complicated VO were longer treated with antibiotics parenterally and more often surgically treated for phlegmon and abscess formation. Liver cirrhosis and degenerative spine disease, which were more often found in patients with complicated VO, obviously impacted the course of the disease.