OBJECTIVE: Hemophilia is associated with a high prevalence of disabilities and mortality. This finding can be influenced by patient compliance with the treatment protocol. This study aims to identify compliance with a treatment protocol in adult patients with hemophilia and to evaluate the factors associated with and the impact on mortality of noncompliance with a hemophilia treatment protocol. METHODS: This was a cross-sectional study that was performed between June 2015 and May 2016, followed by a cohort to evaluate mortality until July 2019 that included all adult patients with hemophilia registered in the Federal District, Brazil. RESULTS: Among 138 patients enrolled in the study, 35 patients were compliant with all items of the treatment protocol (25.4%). Regarding each item, compliance with the medical consultations was 71.0% (98/138); the clotting factor regimen was 65.9% (91/138); and the serological tests were 51.4% (71/138). The mortality was 7.2% (10/138). Noncompliance with any aspect of the protocol was associated with mortality: medical consultations (p<0.001), clotting factor regimen (p=0.013), and serological tests (p=0.006). All deaths occurred in those who did not comply with the protocol, and the majority were due to bleeding. Patients who were noncompliant with all protocol items showed the highest mortality (50.0%, 5/10). Treatment at the hemophilia treatment center (OR: 2.388; 95% CI: 1.052-5.418, p=0.037) was positively and independently associated with compliance with the protocol in multivariate analysis. CONCLUSION: Noncompliance with the treatment protocol was high. Treatment at a hemophilia treatment center was positively and independently associated with compliance with the protocol, which reinforces the importance of comprehensive care by a multidisciplinary team.