Early diagnosis and proper treatment of pyogenic vertebral osteomyelitis (PVO) in patients with cirrhosis is challenging to clinicians, and the mortality rate is expected to be high. A retrospective study was conducted to investigate the treatment outcome in PVO patients with cirrhosis and to identify the predictors of their mortality. Mortality was divided into two categories, 30-day and 90-day mortality. A stepwise multivariate logistic regression model was used to identify predictors of mortality. Eighty-five patients were identified after initial exclusion. The patients' mean age was 60.5 years, and 50 patients were male. The early mortality rates within 30 and 90 days were 17.6% and 36.5%, respectively. Multivariate analysis revealed that increased age, CTP class C, and bacteremia at the time of PVO diagnosis were predictors of 30-day mortality, while higher MELD score, presence of combined infection, and multiple spinal lesions were predictors of 90-day mortality. Attention should be paid to the high mortality between 30 and 90 days after PVO diagnosis (18.8%), which was higher than the 30-day mortality. Liver function was consistently a strong predictor of mortality in PVO patients with cirrhosis. The high-risk patients should be targeted for an aggressive diagnostic approach, using spinal MRI and intensive monitoring and treatment strategies.