OBJECTIVES: To examine the relationship between average daily dose (ADD) of duloxetine, medication adherence, and healthcare costs among fibromyalgia patients. METHODS: This study employed a retrospective cohort design to analyze administrative claims database for commercially-insured patients diagnosed with fibromyalgia who initiated duloxetine in 2006, with initiation defined as 90-day medication gap. The dispense date of the first duloxetine prescription filled was defined as the index date. All patients selected were required to have at least 30 days of duloxetine supply in the 12 months follow-up period, and those with diabetic peripheral neuropathic pain or depression diagnosis during the prior 12 months were excluded. Five cohorts were constructed based on ADD: <30mg, 30mg, 31-59mg, 60mg, and >60mg. Adherence was measured via medication possession ratio (MPR) of duloxetine over 12-month post-index period, with MPR=0.8 as high adherence. Multivariate regression models adjusting for differences in demographic and clinical characteristics were used to examine the association between ADD, adherence and healthcare costs. RESULTS: The study sample included 4,869 fibromyalgia patients. Three percent of patients had an ADD of <30mg, 12% of 30mg, 21% of 31-59mg, 46% of 60mg, and 18% of >60mg. Approximately one-third of patients had high adherence. Controlling for demographics and clinical characteristics, patients with ADD =30mg (31-59mg, and >60mg) were less (more) likely to adhere to duloxetine than those with 60mg (all p<0.05). Compared with patients maintaining an ADD of 60mg, those with ADD of 31-59 mg or >60 mg had significantly higher total health care costs ($1835 and $5490, respectively, both p<0.05), while those with an ADD of 30mg had significantly lower costs (-$1853, p<0.05). CONCLUSIONS: Fibromyalgia patients with an ADD > 30mg of duloxetine were more likely to adhere to the therapy. Maintaining an ADD of 30 and 60mg was associated with reduced total health care costs.