STUDY DESIGN: Triple blind randomized controlled study. OBJECTIVE: To establish the treatment effect of etanercept in acute sciatica secondary to lumbar disc herniation. SUMMARY OF BACKGROUND DATA: Etanercept is a selective competitor of tumor necrosis factor-alpha which is a proinflammatory cytokine. It is currently used alone or in combination with other medication for the treatment of chronic inflammatory disease. METHODS: Inclusion criteria were acute unilateral radicular leg pain secondary to herniated nucleus pulposus confirmed on magnetic resonance imaging scan. Exclusions were previous back surgery, spinal stenosis and any contraindications to the use of etanercept such as immunosuppression. The patient, the injector, and assessor were blinded to the agent being used. Follow-up was at 6 weeks and 3 months posttreatment. Oswestry disability index and visual analog scores were among the assessment criteria. RESULTS: Fifteen patients were recruited in a 4 years period with a 3 months follow-up of 80%. The etanercept group had 8 patients whereas the placebo group had 7. The average Oswestry disability index for the etanercept group preintervention was higher than that in the placebo group (53.6 vs. 50.4) and this remained the same after 6 weeks (46.1 vs. 31.2) and 3 months of follow-up (37 vs. 35). Visual analog score was also higher in the etanercept group versus placebo; preinjection (8.6 vs. 7.4), 6 weeks (5.0 vs. 3.8), and 3 months (4.8 vs. 4.5). CONCLUSIONS: Small numbers of trial participants limited statistical analysis. The trend appears to show no benefit to the use of etanercept over placebo in the pharmacologic treatment of sciatica.