The objective of this study is to perform a cost-utility analysis to estimate the incremental cost-effectiveness ratio (ICER) of oral sumatriptan versus oral ergotamine/caffeine in patients with moderate-to-severe episodic migraine. Additionally, the ICER per block of pain freedom at 2 hours was evaluated. This study estimates the cost-effectiveness of oral sumatriptan versus oral ergotamine/caffeine using a decision tree model over a 30-day time horizon, adopting the payer perspective. The model incorporates one switch between the two therapies. The cohort reflects adults enrolled in randomized, placebo-controlled trials. Costs and utilities were obtained from previously published cost-effectiveness studies. One-way sensitivity analyses were conducted to test the robustness of the results. From the payer perspective, sumatriptan is more costly and more effective than ergotamine/caffeine, with an ICER of $10,466 per QALY gained and an ICER of $3,874 per 2-hour headache freedom achieved. After varying input parameters by 20%, the top three parameters with the greatest impact on the model were the cost of side effects (nausea/vomiting), probability of switching from ergotamine/caffeine to sumatriptan, and probability of 2-hour headache freedom on sumatriptan. Results were robust to sensitivity analyses. For individuals with moderate to severe episodic migraine, oral sumatriptan may be more cost-effective than oral ergotamine/caffeine.