OBJECTIVES: To examine whether duloxetine initiators had different medication compliance or health care costs than pregabalin initiators among elderly patients with fibromyalgia. METHODS: A large, US national claims database was analyzed to identify fibromyalgia patients aged 65 and above with Medicare supplemental insurance who initiated duloxetine or pregabalin in 2006. Initiation was defined as no pill coverage in the previous 90 days, with the first initiation date as the index date. All selected patients had 12-month continuous enrollment before and after the index date. Duloxetine initiators with diabetic peripheral neuropathic pain (DPNP) or depression, and pregabalin initiators with DPNP, post-herpetic neuralgia or epilepsy diagnosis in the 12-month pre-index period were excluded. Propensity scoring was applied to construct the duloxetine and pregabalin cohorts controlling for differences in demographics, pre-index clinical and economic characteristics, and pre-index treatment patterns. Medication compliance (i.e., medication possession ratio (MPR), proportion of patients with MPR≥80%), and health care costs over the first 12-month post-index period were examined between cohorts. RESULTS: Patients in the duloxetine (n=614) and pregabalin (n=1188) cohorts had a mean age of 75 years. The most common comorbid conditions in both cohorts were cardiovascular disease (88.1% vs. 85.8%), neuropathic pain other than DPNP (72.5% vs. 72.2%), low back pain (71.6% vs. 71.3%), and osteoarthritis (57.4% vs. 57.5%), while opioids (83.3% vs. 83.0%) were the most commonly prescribed medication over the 12 months pre-index period. Adjusting for demographics, pre-index clinical and economic characteristics, and prior medication history, duloxetine initiators had significantly higher MPR (0.70 vs. 0.56, p<0.05), higher proportion of patients with MPR≥0.8 (44.8% vs. 29.0%, p<0.05), and significantly lower total healthcare costs ($26,323 vs. $27,112, p<0.05) over the 12-month post-index period than pregabalin patients. CONCLUSIONS: Among elderly fibromyalgia patients, duloxetine initiators had better medication compliance and lower direct health care costs than pregabalin initiators.