OBJECTIVES: Medication adherence and persistence are important in the treatment of fibromyalgia. The objective of this study is to examine the predictors of adherence and persistence to duloxetine therapy among commercially-insured fibromyalgia patients. METHODS: This study analyzed medical and pharmacy records for commercially-insured patients aged 18-64 with fibromyalgia who initiated (no prior 90-day use) duloxetine in 2008. Patients selected had continuous health insurance enrollment for 12 months preceding and following duloxetine initiation, at least 1 fibromyalgia diagnosis during the 12 months before, or 1 month after, the initiation date, and at least 30-day cumulative duloxetine supply over the 12-month post-index period. Adherence to duloxetine was measured by medication possession ratio (MPR = post 1-year total duloxetine supply days/365), with high adherence defined as MPR ≥0.8. Persistence was defined as the length of therapy (LOT) from the index date to the earliest of the ending date of the last prescription, the date of the first gap of more than 15 days between prescriptions, or the end of study period (12 months). Demographic and clinical predictors of adherence and persistence were examined via multivariate logistic regression (MLR) and classification and regression trees (CART). RESULTS: Among 4,660 duloxetine patients, 33% achieved high adherence. Factors associated with high adherence from MLR included older age, North Central and Northeast regions, prior venlafaxine, pregabalin, SSRIs or other antidepressants use, or comoribid dyslipidemia, osteoarthritis, or skin and subcutaneous tissue disorders (all p<0.05). CART analysis revealed that patients with prior use of antidepressants, age ≥46, or prior osteoarthritis disorder had higher MPR  (all p<0.05), and patients aged ≥45 with a history of SSRI, venlafaxine or anticonvulsant use had longer LOT (all p<0.05). CONCLUSIONS: One-third of fibromyalgia patients on duloxetine achieved high adherence.  Patients with high adherence and persistence to duloxetine were significantly older and had prior antidepressant use.