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Introduction: Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%–48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis. Research question: The purpose of this study is to determine differences in pathogen identification and clinical outcomes for PEDD versus CT-guided needle biopsy in SD patients. Materials and methods: We conducted a systematic review of the literature using PRISMA guidelines to determine differences in positive microbiology results, perioperative complications, pain control, and long-term clinical outcomes for PEDD vs. CT-guided needle biopsy in SD patients. Results: 1078 studies were evaluated, 87 of which underwent full review. 15 studies met the inclusion and exclusion criteria, including 7 PEDD, 7 CT-guided biopsy, and 1 CT-guided biopsy vs. PEDD article, for a total of 192 PEDD patients and 604 CT-guided biopsy patients. We found 36.59% of CT-guided biopsy patients had positive microbiology results, compared to 84.38% of PEDD patients. No major perioperative complications occurred as a result of the PEDD procedure. Of the five PEDD studies that reported pain outcomes, greater than 80% of patients experienced relief after intervention. Discussion and conclusion: These results suggest that PEDD may improve pathogen identification while simultaneously reducing pain compared to CT-guided needle biopsy in SD. Although current treatment guidelines recommend CT-guided biopsy, in patients with severe back pain and suspected SD, PEDD can be considered an alternative intervention.