This report is the second surveillance report for the Agency for Healthcare Research and Quality (AHRQ) 2020 report Acute Treatments for Episodic Migraine (available at https://effectivehealthcare.ahrq.gov/products/migraine-treatments/research) and covers the time period from September 2, 2021, through December 30, 2021. The original 2020 report examined the evidence on the comparative effectiveness and harms of opioids as well as nonopioid pharmacologic and nonpharmacologic treatments to provide the full range of evidence to inform clinical decision making about the acute treatment of migraine. The objectives of this surveillance report are to identify the latest evidence published since the last surveillance report as of September 2, 2021 (Surveillance Report 1), and to determine how the new evidence impacts the findings of the 2020 report and surveillance report. Another update is planned for June 2022 (based on evidence published from January to March 2022).