OBJECTIVES Although opioids have not demonstrated efficacy in treating fibromyalgia (FM) and pose a risk for addiction, they are commonly used to treat FM patients. This study assesses the mean annual per patient cost of FM-related opioid use in commercially insured FM patients. METHODS Using the Thomson/Medstat MarketScan Commercial Claims Database, we identified all patients aged 18+ years with continuous health plan eligibility in 2006 and ≥1 inpatient or ≥2 outpatient paid medical claims in calendar year 2006 with ICD-9-CM diagnosis code 729.1 ("FM patients"). Rx medications designated as possibly related to FM treatment ("FM-related") included opioids, anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate analgesics, antimigraine agents, muscle relaxants, corticosteroids, benzodiazepines, sedatives/hypnotics, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), and selective serotonin reuptake inhibitors (SSRIs). Mean annual costs per patient were calculated using third-party payments for Rx drug claims. RESULTS A total of 77,124 patients met all study entry criteria. Of these FM patients, 40,951 (53.1%) had evidence of receipt of opioids in 2006. Total mean annual Rx drug costs per patient were $2225.92. FM-related Rx drugs represented $912.80 (41.0%) of these costs. Opioids were the most costly drug class, accounting for $272.79 (29.9%) of FM-related Rx drug costs. The next most costly drug class was anticonvulsants at $112.90 (12.4%), followed by SNRIs at $105.14 (11.5%) and SSRIs at $78.53 (8.6%). CONCLUSIONS Given the widespread use of opioids, their lack of efficacy, and their potential for addiction, reducing opioid use may benefit patients and reduce costs. New disease management methods and more effective medications to treat FM may assist in achieving this goal.