Migraine is a debilitating condition that affects approximately 16% of adults and is the fifth leading cause of emergency department visits in the United States. There are several treatment options for migraines; opioids are frequently prescribed. Results from a recent study showed that more than half of the patients with chronic migraine and a third of the patients with episodic migraine received an opioid prescription in the past year. The American Headache Society recognizes the magnitude of this issue and is working to educate providers on the danger of prescribing opioids in the migraine population The objective of this article is to assess the utilization trends of prescription opioid products and evaluate the impact of opioid utilization on healthcare costs in this patient population. This retrospective claims database analysis used real-world medical claims from multiple health plans. The study period was from January 1, 2009, to September 30, 2017. Patients were included if they were 18 years or older and continuously enrolled in the study period for at least 3 years. Patients were included in the migraine cohort if they had any diagnosis of migraine headache during the study period, while patients without a headache related diagnosis were included in the control cohort. Control patients were propensity matched 1:1 to migraine patients. Discrete (count) data are represented by frequencies and percentages. Continuous results are presented as means, medians, and standard deviations. In the study, 107,216 patients met the inclusion criteria, with 53,608 assigned to each cohort. In the migraine and control cohorts, respectively, 28% and 11% were prescribed opioids. In both cohorts, a majority of the patients were female (81.8%). In both cohorts, opioid use was associated with higher total costs compared with patients who were not prescribed opioids: $82,007 for 200 morphine milligram equivalents (MME)/day or more versus $19,792 for no opioid in patients with migraine; and $54,200 for 200 MME/day or more versus $12,060 for no opioid use in control patients; P <.0001. Patients with more than 2 comorbidities who were prescribed opioids had higher costs than patients with more than 2 comorbidities who were not prescribed opioids and patients with less than 2 comorbidities who were prescribed opioids ($65,980, $32,152, and $35,964, respectively, for patients with migraine, and $52,883, $24,641, and $35,748, respectively, for control patients; P <.0001). Patients with migraine have more than twice the healthcare costs as patients without migraines. The additional increase in healthcare costs in patients with migraine who use opioids for treatment and/or have 2 or more comorbidities is significant. Control of the pain associated with migraine, specifically among those with multiple comorbid conditions, may contribute to substantial reductions in healthcare costs.