OBJECTIVES: Early intervention in the course of acute migraine attacks has been recently advocated as a way to further reduce the economic burden and suffering of patients due to this condition. The aim of this study was to investigate the cost-effectiveness of such a strategy using almotriptan in the Spanish setting. METHODS: An economic evaluation was conducted from the Spanish societal and public health system perspective based on patient-level data collected in the “Act when Mild” study. Incremental cost-effectiveness ratios (ICER) were determined in terms of attack duration, loss of productive time and quality-adjusted life days (QALDs). Monte Carlo simulation was used to derive cost-effectiveness acceptability curves. RESULTS: Early treatment led on average to shorter attack duration, less productive time lost, better quality of life, and was overall cost-saving from a societal point of view with a probability of 97%. In terms of publicly reimbursed drug costs only, though, non-early treatment was always slightly less expensive. From the public health system perspective the (bootstrap) mean ICER of early treatment amounted to €0.12 per migraine hour avoided, €0.42 per hour of productive time lost avoided, and €6.62 per QALD gained. Considering willingness to pay values of €1 to reduce attack duration by one hour, €5 to avoid the loss of one productive hour, or €55 to gain one QALD (equivalent to €20,000 per QALY), the probability that early treatment was cost-effective from the public health system perspective was, respectively, 96%, 96%, and 98%. These results remained robust in sensitivity analyses that accounted for the uncertainty surrounding the major elements of the economic evaluation. CONCLUSIONS: Compared to non-early treatment, early treatment of acute migraine attacks with almotriptan when pain is still mild is with high probability cost-saving from the Spanish societal perspective and cost-effective from the public health system point of view.