The aim of this paper is to estimate the relative cost-effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed, based on information from the findings from a systematic review of clinical and cost-effectiveness, published sources of unit costs and expert opinion. The assumption was patients presenting with sciatica would be managed through one of three pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12 month period. One-way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was non-opioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was non-opioids, followed by biological agents, followed by epidural/nerve block and disc surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost-effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per QALY are higher, the economic model demonstrated that stepped approaches based on initial treatment with non-opioids are likely to represent the most cost-effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required.