Aim of this prospective randomized trial was to analyze the effectiveness of MESNA in chemical dissection of peridural fibrosis in patients who underwent revision lumbar spine surgery. Between January 2003 and October 2006, 30 patients who underwent revision lumbar spine surgery were enrolled in the study. Patients were randomly assigned to one of two groups: a study group (A) and a control group (B). Once peridural fibrosis was exposed, MESNA (Uromixetan MESNA, 50 mg/ml) was intraoperatively applied on the fibrous tissue (Group A) to ease tissue dissection and enter the canal. In patients of Group B, saline solution was used. Surgical time, preoperative and 1 week postoperative hemoglobin (Hb), length of hospitalization (days), and incidence of perioperative complications were evaluated. The blinded surgeon assigned the surgeries to one of four categories as none, minimal, moderate, and severe basing on intraoperative difficulty in dissecting the fibrous tissue and intraoperative bleeding. Statistical analysis used chi-square analysis to evaluate the difference in surgery difficulty and the incidence of intraoperative complications between the two groups. The analysis of surgical time and hemoglobin levels was performed using a one-sample Wilcoxon test and Mann-Whitney U test. Patients in whom MESNA was used intraoperatively (Group A) presented better intraoperative and perioperative parameters with respect to the control group. Average surgical time and decrease in Hb postoperatively were more in the saline group (B) respect to MESNA (A) (P = 0.004 and P = 0.001, respectively), while no difference in average hospital stay was reported between the two groups. Surgeon-blinded intraoperative report on surgical difficulty showed a significant difference between the two groups (P < 0.05). Postoperatively, no complications directly attributable to the use of MESNA were experienced. The incidence of dural tears and intraoperative bleeding from epidural veins were significantly less in Group A with respect to the control group. MESNA contributed significantly to reduce the operative complications, with a diminution of the surgical time and the grade of difficult for the surgeon, confirming its ability as chemical dissector also for epidural fibrosis in revision lumbar spine surgery.