Background: Rheumatic heart disease (RHD) remains a leading cause of morbidity and mortality in sub-Saharan Africa despite widely available preventive therapies. In this study, we sought to characterize facilitators and barriers to RHD treatment in Sudan. Methods: We conducted a mixed-methods study, collecting survey data from 398 patients who had enrolled in a national RHD registry between July and November 2017. The surveys included information on demographics, healthcare access, and patient perspectives on treatment barriers and facilitators. Factors associated with increased likelihood of RHD treatment adherence were assessed using multivariate logistic regression. These data were enhanced by focus group discussions with 20 participants, further exploring health system factors impacting RHD care. Results: Our analysis revealed that female gender (Odds ratio (OR) = 1.94; 95% CI 1.14-3.29), increased household income (monthly income above 2000 Sudanese pounds; OR = 2.02; 95% CI 1.26-3.25), and a perceived appropriate level of healthcare staffing by doctors and nurses (OR = 2.07; 95% CI 1.16-3.71) were all factors associated with increased odds of treatment adherence. Further, qualitative data revealed significant barriers to RHD treatment arising from health services factors at the systemic level: The primary barriers to RHD treatment included patient lack of understanding of disease, lack of access due to inadequate healthcare staffing, lack of faith in local healthcare systems, and poor ancillary services. Facilitators of RHD treatment included stronger interpersonal support.Conclusions: Enhancing RHD patient education/engagement, while strengthening local health systems, may lead to improved treatment adherence in this vulnerable population.