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Objective: To describe treatment patterns and direct healthcare costs over 3 years following initiation of standard of care acute and preventive migraine medications in patients with migraine in the United States. Background: There are limited data on long‐term (>1 year) migraine treatments patterns and associated outcomes. Methods: This was a retrospective, observational cohort study using US claims data from the IBM® MarketScan® Research Database (January 2010–December 2017). Adults were included if they had a prescription claim for acute migraine treatments (AMT) or preventive migraine treatments (PMT) in the index period (January 2011–December 2014). The AMT cohort was categorized as persistent, cycled, or added‐on subgroups; the PMT cohort was categorized PMT‐persistent, switched without gaps, or cycled with gaps. Migraine‐specific annual direct costs (2017 US$) across AMT and PMT cohort subgroups were summarized at baseline through 3 years from index (follow‐up). Results: During the index period, 20,778 and 42,259 patients initiated an AMT and a PMT, respectively. At the 3‐year follow‐up, migraine‐specific direct costs were lower in the persistent subgroup relative to the non‐persistent subgroups in both AMT (mean [SD]: $789 [$1741] vs. $2847 [$8149] in the added‐on subgroup and $862 [$5426] for the cycled subgroup) and PMT cohorts (mean [SD]: $1817 [$5892] in the persistent subgroup vs. $4257 [$11,392] in the switched without gaps subgroup and $3269 [$18,540] in the cycled with gaps subgroup). Acute medication overuse was lower in the persistent subgroup (1025/6504 [27.2%]) vs. non‐persistent subgroups (11,236/58,863 [32.2%] in cycled with gaps subgroup and 1431/6504 [39.4%] in the switched without gaps subgroup). Most patients used multiple acute (19,717/20,778 [94.9%]) or preventive (38,494/42,259 [91.1%]) pharmacological therapies over 3 years following treatment initiation. Gaps in preventive therapy were common; an average gap ranged from 85 to 211 days (~3–7 months). Conclusion: Migraine‐specific annual healthcare costs and acute migraine medication overuse remained lowest among patients with persistent AMT and PMT versus non‐persistent treatment. Study findings are limited to the US population. Future studies should compare costs and associated outcomes between newer preventive migraine medications in patients with migraine. Plain Language Summary: Little is known about how patients use medications to acutely treat or prevent migraine over longer periods of time and their associated costs. This study used information from medical and pharmacy claims to understand costs over time for three groups of patients with migraine: (1) those who remained on the same medication for 3 years, (2) those who changed medications, or (3) those who stopped treatment and then changed medications. Results showed that fewer than one in 10 patients stayed on the same medication to treat or prevent migraine over 3 years, but migraine costs and acute migraine medication overuse were lowest in these patients. [ABSTRACT FROM AUTHOR]