Purpose Vertebral osteomyelitis (VO) is a severe clinical entity associated with significant morbidity and mortality. Several studies have showed that successful treatment of VO patients leads to significantly improved quality of life (QoL). Nevertheless, QoL levels of these patients remained below those of the general population. There are rarely studies focusing on predicting factors for favourable QoL after surgically treated VO. The aim of this study was to identify factors influencing positively the QoL of patients undergoing surgery for VO. Methods We conducted a prospective monocentric study including surgically treated VO patients from 2008 to 2016. Data were collected before (T0) and 1 year (T1) after surgery. Primary outcome was favourable QoL defined as back pain with disability restricting normal life activity with a cutoff value ≥ 12 on Oswestry Disability Index (ODI). Ethics Ethical approval was given by the Faculty of Medicine at the University of Cologne (09-182). Results A total of 119 patients surviving 1 year after surgically treated VO were analysed. Favourable QoL was achieved in 35/119 patients. On multivariate analysis, younger age (hazard ratio = HR: 0.95; 95% CI 0.91–0.99; p = 0.022), lower albumin (HR: 0.9; 0.83–0.98; p = 0.019) an ASA score ≤ 2 (HR:4.24; 95%CI 1.42–12.68; p = 0.010), and a lower preoperative leg pain on the VAS (HR: 0.86; 95% CI 0.76–0.97; p = 0.018) were identified as independent risk factors for favourable QoL. Interestingly, the absence of neurological deficits was not predictive for a favourable outcome by means of QoL. Conclusion One-third of surgically treated VO patients (29%) in our cohort achieved favourable QoL by means of ODI. Our findings can facilitate an estimation of the prognosis when informing the patient before surgery, and underscore that spine disability questionnaires, such as ODI, measuring QoL, are mandatory to evaluate comprehensively the outcome of this entity.