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Interbody fusion represents an efficient surgical treatment in degenerative lumbar disease, achieving satisfying outcome in >90% of cases. Various studies have affirmed the advantages of percutaneous and minimally invasive techniques with regard to minimized damage on soft tissues during surgical procedure, but their efficacy in comparison with the classic open surgical procedures has not yet been demonstrated.This is a retrospective study. We compared 30 consecutive patients affected by disk degenerative disease or grade I degenerative spondylolisthesis that were treated with minimally invasive transforaminal lumbar interbody fusion (mini-TLIF) to a group of 34 consecutive patients presenting similar pathologic findings and demographic characteristics that underwent interbody fusion by traditional open approach (open-TLIF). All patients were treated between 2006 and 2010. Patients’ mean age was 46 years (min 28–max 56) and 51 years (min 32–max 58), respectively. Mean follow-up was 23 months (min 12–max 38) and 25 months (min 12–max 40), respectively. Clinical evaluation was performed by using Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) questionnaires. Radiographic evaluation was performed on standing and dynamic x-rays before operation and at final follow-up.There was a statistically significant improvement in clinical scores (VAS and ODI) in both groups. Early postoperative VAS score was significantly lower in the mini-TLIF group. Mean hospital stay and mean blood loss were significantly higher in the open-TLIF group than in the mini-TLIF group (7.4 vs. 4.1 d and 620 vs. 230 mL, respectively). Surgical time length of the procedure was higher in the mini-TLIF group. There were no major neurological complications in any of the patients. At final follow-up, radiographic evaluation showed good implant stability in both groups.Mini-TLIF is a safe and efficient procedure and, when correctly and carefully performed, can reach good results, similar to those obtained with traditional open surgical techniques, even though it may require a longer surgical time at least during the first stages of the learning curve. Reduced surgical invasiveness, short hospital stay, and limited blood loss represent the major advantages of minimally invasive technique.