OBJECTIVES: The aim of this research was to evaluate the cost-effectiveness of duloxetine as an additional treatment option in the management of fibromyalgia (FM), assessed from an NHS Scotland health care system perspective. METHODS: We used a 3-year health state transition model to represent the sequential drug management of patients with FM. Guidelines, evidence reviews and clinical opinion were used to define a standard treatment for Scotland based on tricyclic antidepressants (TCAs) with switching to second-generation antidepressants (SSRIs or SNRIs). The model considered two levels of pain response based on an 11-point severity scale (0=‘no pain’ to 10=‘worst pain possible’):  ≥30-% (response) and ≥50% (full response) change from baseline score. Clinical efficacy and discontinuation data were taken from a systematic literature review and an adjusted indirect meta-analysis based on placebo-controlled trials of FM treatments. Utility data were linked to pain severity using trial-based EQ-5D data collected from patients in the duloxetine studies. Costing was based on 2006. Annual discounting was applied equally at 3.5%. RESULTS: The first-line use of duloxetine resulted in approximately 67 additional quality-adjusted life years (QALYs) per 1000 patients, achieved at an additional cost of £397,360. This corresponded to a cost per QALY of £5950 compared to current standard treatment without duloxetine. These results were robust to both deterministic and probabilistic sensitivity analyses, demonstrating a 70% probability of the ICER falling below £15,000 per QALY. A step-wise analysis reported a cost per QALY of £4847 for first-line duloxetine versus second-line treatment and £7360 versus third-line treatment. CONCLUSIONS: There is currently a significant unmet need for patients with poorly controlled FM where pain is a predominant symptom. These analyses show that the introduction of duloxetine into the standard treatment sequence for FM could provide additional patient benefits which should be considered cost-effective when compared to commonly adopted thresholds.