Older patients with pyogenic vertebral osteomyelitis (PVO) usually have more medical comorbidities compared with younger patients, and present with advanced infections from different causative organisms. To aid surgical decision-making, we compared surgical outcomes of older patients with PVO to those who underwent nonoperative treatment. We identified the risk factors for adverse post-operative outcomes, and analyzed the clinical risks from further spinal instrumentation. This retrospective comparative study included 439 patients aged ≥75 years with PVO. Multivariable analysis was performed to compare treatment outcomes among three groups: 194, 130, and 115 patients in the non-operative, non-instrumented, and instrumented groups, respectively. The risk factors for adverse outcomes after surgical treatment were evaluated using a logistic regression model, and the estimates of the multivariable models were internally validated using bootstrap samples. Recurrence and mortality of these patients were closely associated with neurologic deficits, and increased surgical invasiveness, resulting from additional spinal instrumentation, did not increase the risk of recurrence or mortality. We propose that surgical treatment for these patients should focus on improving neurologic deficits through immediate and sufficient removal of abscesses. Spinal instrumentation can be performed if indicated, within reasonable clinical risk.