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Background Minimally invasive transforaminal lumbar interbody fusion (TLIF) has undergone significant evolution since its conception as a fusion technique to treat lumbar spondylosis. Minimally invasive TLIF is commonly performed using intraoperative two-dimensional fluoroscopic x-rays. However, intraoperative computed tomography (CT)–based navigation during minimally invasive TLIF is gaining popularity for improvements in visualizing anatomy and reducing intraoperative radiation to surgeons and operating room staff. This is the first study to compare clinical outcomes and cost between these 2 imaging techniques during minimally invasive TILF. Methods For comparison, 28 patients who underwent single-level minimally invasive TLIF using fluoroscopy were matched to 28 patients undergoing single-level minimally invasive TLIF using CT navigation based on race, sex, age, smoking status, payer type, and medical comorbidities (Charlson Comorbidity Index). The minimum follow-up time was 6 months. The 2 groups were compared in regard to clinical outcomes and hospital reimbursement from the payer perspective. Results Average surgery time, anesthesia time, and hospital length of stay were similar for both groups, but average estimated blood loss was lower in the fluoroscopy group compared with the CT navigation group (154 mL vs. 262 mL; P = 0.016). Oswestry Disability Index, back visual analog scale, and leg visual analog scale scores similarly improved in both groups ( P > 0.05) at 6-month follow-up. Cost analysis showed that average hospital payments were similar in the fluoroscopy versus the CT navigation groups ($32,347 vs. $32,656; P = 0.925) as well as payments for the operating room ( P = 0.868). Conclusions Single minimally invasive TLIF performed with fluoroscopy versus CT navigation showed similar clinical outcomes and cost at 6 months. [ABSTRACT FROM AUTHOR]