Only 6 cases of pyogenic spondylitis following vertebroplasty or kyphoplasty have been reported, and their causes remained unclear. The authors report on 4 cases of delayed pyogenic spondylitis (DPS) following vertebroplasty or kyphoplasty for osteoporotic compression fractures and metastatic disease. Four patients presented with DPS after vertebroplasty or kyphoplasty and underwent surgical treatment. Clinical history, laboratory examination, and MR imaging confirmed the diagnosis of DPS. Anterior debridement, reconstruction, and posterior instrumented fusion were performed. The mean interval for the delayed occurrence of pyogenic spondylitis after surgery was 12.3 months. The infections were primarily bacterial in origin, but most patients also suffered diverse medical comorbidities. Despite successful treatment of the infections, comorbidity was and is a factor that compromises good results. Medical comorbidities associated with compromised immunity may increase susceptibility to DPS after vertebroplasty or kyphoplasty. In cases of incapacitating back pain after a pain-free period following either of these surgeries, evaluation of the erythrocyte sedimentation rate and C-reactive protein level and examination of contrast-enhanced MR imaging studies are essential to rule out delayed vertebral infection. Surgical treatment requires cement removal and anterior reconstruction with or without additional posterior instrumented fusion.