Surgical procedures with spinal instrumentation constitute a prevalent and occasionally highly indicated treatment modality in patients with pyogenic spondylodiscitis (PSD). However, surgical therapy might be associated with the need of prolonged postoperative intensive care medicine which in turn might impair intended operative benefit. Therefore, we analyzed prolonged mechanical ventilation (PMV) as an indicator variable for such intensive care treatment with regard to potential correlations with mortality in this vulnerable patient cohort. Between 2012 and 2018, 177 consecutive patients received stabilization surgery for PSD at the authors’ neurosurgical department. PMV was defined as postoperative mechanical ventilation of more than 24 h. A multivariable analysis was performed to identify independent predictors for 30-day mortality. Twenty-three out of 177 patients (13%) with PSD suffered from postoperative PMV. Thirty-day mortality rate was 5%. Multivariable analysis identified “spinal empyema” (p= 0.02, odds ratio (OR) 6.2, 95% confidence interval (CI) 1.3–30.2), “Charlson comorbidity index (CCI) > 2” (p= 0.04, OR 4.0, 95% CI 1.0–15.5), “early postoperative complications (PSIs)” (p= 0.001, OR 17.1, 95% CI 3.1–96.0) and “PMV > 24 hrs” (p= 0.002, OR 13.0, 95% CI 2.7–63.8) as significant and independent predictors for early postoperative mortality. The present study indicates PMV to significantly correlate to elevated early postoperative mortality rates following stabilization surgery for PSD. These results might entail further scientific efforts to investigate PMV as a so far underestimated negative prognostic factor in the surgical treatment of PSD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10143-023-02016-1.