Introduction: In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2–4 prior preventive migraine treatment failures. This post hoc analysis evaluated the efficacy of eptinezumab across the 24-week placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure type. Methods: DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously every 12 weeks. Changes from baseline in MMDs and percentages of patients with ≥ 50% reduction from baseline in MMDs (≥ 50% migraine responder rates [MRRs]) were summarized in subgroups of patients defined by prior treatment failure type. Subgroups were not mutually exclusive and included patients for whom topiramate, beta blockers (metoprolol, propranolol), amitriptyline, and/or flunarizine had failed. Results: Across Weeks 1–12 in all subgroups, patients treated with eptinezumab experienced greater reductions from baseline in MMDs than those receiving placebo (reductions ranged from 4.5–5.5 vs 1.6–2.4, respectively), with larger reductions over Weeks 13–24. Similarly, ≥ 50% MRRs were consistently higher with eptinezumab than placebo and increased following a second infusion. Conclusion: In all subgroups, regardless of prior preventive treatment failure type, eptinezumab demonstrated greater reductions in MMDs and higher MRRs compared with placebo. Trial Registration: ClinicalTrials.gov (Identifier: NCT04418765).