OBJECTIVE: To evaluate the effect of hyaluronidase in patients with failed back surgery syndrome (FBSS) treated with interlaminar lumbar epidural injection (ILEI). METHOD: Sixty patients suffering from severe low back pain and sciatica were randomly allocated into three groups. Group T received ILEI with 2 ml triamcinolone 40 mg/ml and 5 ml bupivacaine 0.25%. Group H received ILEI with 1500 IU hyaluronidase and 5 ml bupivacaine 0.25%. Group TH received interlaminar lumbar epidural injection (ILEI) with 1500 IU hyaluronidase, 2 ml triamcinolone 40 mg/ml and 5 ml bupivacaine 0.25%. The effect was evaluated using Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) at pre-injection, 2 weeks, 6 weeks and 12 weeks after ILEI. RESULTS: After 2 weeks and after 6 weeks, patients in both Group T and Group TH had significant effectiveness more than Group H in decrease of VAS and ODI. After 12 weeks, only patients in Group TH had significant effectiveness in decrease of VAS and ODI (p<0.05). In every period, Group TH had the most effectivess in decrease of VAS and ODI after ILEI. CONCLUSION: ILEI for FBSS with triamcinolone and hyaluronidase is considered to have more long term effectiveness to reduce pain and improve function after ILEI than injection with triamcinolone alone or hyaluronidase alone.