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Objective Surgical treatment of severe infectious spondylodiskitis remains challenging. Although minimally invasive percutaneous endoscopic drainage and debridement (PEDD) may yield good results in complicated cases, outcomes of patients with extensive structural damage and mechanical instability may be unsatisfactory. To address severe infectious spondylodiskitis, we have developed a surgical technique called percutaneous endoscopic interbody debridement and fusion (PEIDF), which comprises endoscopic debridement, bonegraft interbody fusion, and percutaneous posterior instrumentation. Methods Outcomes of PEIDF in 12 patients and PEDD in 15 patients with infectious spondylodiskitis from April 2014 to July 2018 were reviewed retrospectively. Outcome were compared between 2 kinds of surgical procedures. Results Patients in PEIDF group had significantly lower rate of revision surgery (8.3% vs. 58.3%), better kyphosis angle (-5.73°±8.74 vs. 1.07°±2.70 in postoperative; 7.09°±7.23 vs. 0.79°±4.08 in kyphosis correction at 1 year), and higher fusion rate (83.3% vs. 46.7%) than those who received PEDD. Conclusion PEIDF is an effective approach for treating infectious spondylodiskitis, especially in patients with spinal instability and multiple medical comorbidities.