Objectives: to evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline compliance. Study design: this real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (i.e. after guideline implementation). Results: we included 333 boys in the study cohort. The cumulative incidence of LTP use was 61.2% at three years of age vs. 9.5% in a historical cohort of 39 boys born in 1996 (i.e. before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. LTP was delayed in 10.8% of patients. In the multivariate analysis, two variables were significantly associated with "timely LTP" as compared with "delayed LTP": Hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, p=0.013 vs. Paris Area) and older age at LTP indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, p=0.031) (Figure 3). LTP anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95%CI 0.3-0.8, p=0.010 for birth years 2005-2009 vs. 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95%CI 1.2-3.0, P = .005) were significantly associated with "LTP guideline compliance" vs "LTP anticipation." Conclusions: this study suggests that LTP guidelines are associated with increased LTP use. However, early initiation of LTP remains a challenge.