ObjectivesTo evaluate the methodological quality of guidelines for pharmacological intervention of migraine in adults, to compare and analyze the differences in first-line drug recommendations in different regions and quality levels, so as to explore the evidence of drug recommendations, and provide a basis for clinical decision-making.MethodsPubMed, The Cochrane Library, EMbase, SinoMed, CNKI, VIP, and WanFang Data databases, Up To Date, as well as the related books, Yimaitong, Guideline Central, Guidelines International Network (GIN) and National Institute for Health and Clinical Excellence (NICE) were systematically searched to collect pharmacological intervention guidelines of migraine in adults from inception to January 12th, 2020. The methodological quality of the guidelines was evaluated by Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ).ResultsA total of 25 guidelines were included (including 22 evidence-based guidelines), covering 10 countries on 4 continents and World Health Organization (WHO) with a time span of 1997 to 2019. According to AGREE Ⅱ, 5 were A-level guidelines, 18 were B-level guidelines, and 2 were C-level guidelines. Scope and purpose, rigour of development, clarity of presentations and editorial independence obtained high average scores (more than 60%) among all 25 guidelines. The average scores of guidelines in different domains of AGREE Ⅱ varied with regions and countries. Triptans and NSAIDs were the most frequently recommended as first-line drugs for the acute management; beta-blockers and antiepileptic drugs were recommended for the first-line prevention drugs of migraine in adults. There were 2 guidelines that recommended complementary treatments, one recommended traditional Chinese medicine and another recommended herbal butterbur.ConclusionsThe methodological quality of the pharmacological intervention guidelines of migraine in adults is suboptimal among different regions or countries. The quality of evidence-based guidelines is superior to that established by consensus. The consistency of first-line drug recommendations is strong, but there are still regional differences. The therapeutic effect of traditional Chinese medicine requires further verification.