BACKGROUND AND AIMS: Hemophilia clinical practice guidelines (CPGs) play a vital role in guiding healthcare professionals' decisions. However, the quality and recommendations of CPGs for hemophilia may vary. This study aimed to assess the methodological quality of hemophilia CPGs published between 2017 and 2021 and compare their recommendations for prophylaxis using clotting factor concentrate. METHODS: We conducted a comprehensive search for relevant CPGs in PubMed, TripDatabase, Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) International Guidelines Database, Google Scholar, and Google. We used the AGREE-II instrument to assess the methodological quality of each CPG and compared their recommendations for prophylaxis. RESULTS: Of the 11 CPGs that met the inclusion criteria, 5/11 were developed in upper-middle-income countries, and 6/11 used the GRADE methodology. The primary prophylaxis dose recommendations varied among the CPGs, with 4/11 recommending a low dose, 6/11 recommending an intermediate or high dose, and 1/11 not issuing a recommendation. However, only 2/11 CPGs provided justification for their recommendations on initiation and dose, and no economic evaluations were conducted to support these recommendations. CONCLUSION: The quality of hemophilia CPGs is not optimal, with inconsistent recommendations for prophylaxis and a lack of justification for these recommendations. To ensure evidence-based and trustworthy recommendations, there is a need for transparency and improvement in the decision-making process of hemophilia CPGs.