OBJECTIVES: To examine predictors of adherence to duloxetine therapy and assess the association between adherence and health care costs among working-age patients with fibromyalgia. METHODS: This study analyzed medical and pharmacy records for commercially-insured patients aged 18-64 diagnosed with fibromyalgia who initiated duloxetine between January 1, 2006 and December 31, 2006. The date of first duloxetine prescription filled was defined as the index date. Initiation of treatment was defined as no pill coverage for duloxetine over the prior 90 days. All patients included had at least 30 days supply of duloxetine in the 12 months post-index period. Patients with diabetes peripheral neuropathic pain or depression in the 12 months pre-index period were excluded. Two study cohorts were constructed based on adherence level to duloxetine (high adherence = medication possession ratio of =0.8). Predictors of high adherence were examined via logistic regression. Multivariate regression models were performed to examine the association between adherence and health care costs, controlling for demographics, clinical characteristics, and prior health care costs. RESULTS: A total of 4869 fibromyalgia patients were identified, with a mean age of 50 years and 88% female. Approximately 68% of duloxetine patients had low adherence over the 12 months follow-up period. Higher average daily dose was associated with high adherence (reference group = 30mg; Odds Ratio=3.03, 2.40, and 3.74 for 31-59mg, 60mg, and >60mg, respectively; all p<0.05). Controlling for differences in demographics and clinical characteristics, patients with high adherence had significantly lower total healthcare costs (-$938, p<0.05), primarily due to lower inpatient (-$2,057, p<0.05) and outpatient (-$951, p<0.05) costs than patients with low adherence. CONCLUSIONS: Higher average daily dose of duloxetine appeared to be predictor of high adherence among fibromyalgia patients. High adherence to the duloxetine therapy was associated with lower total health care costs.