Rheumatic heart disease (RHD) is a preventable disease that is prevalent in developing regions of the world. Its eradication from most of the developed world indicates that this disease can be controlled and eliminated. Aim: To conduct an in-depth analysis of the trends and challenges of controlling RHD in the Eastern Mediterranean region (EMR). Methodology: Global data from the World Health Organization (WHO) data banks were retrieved for total deaths and age standardized death rate per 100,000 (ASDR) by age group, sex, and year (from 2000 to 2015). The data was compared with the five other WHO regions of the world. We also performed in-depth analysis by socio-economic groups in relation to other attributes in the region related to population growth, illiteracy, and nutritional status. Indicators of service delivery were correlated with ASDR from RHD. Findings: Prevalence of RHD in 2015 in the EMR region was one-third of that of the total deaths reported in the Asian and West Pacific regions. The total deaths for the region peaked twice: in early adulthood and again later in old age, and was higher in females than in males. There was a rising trend in deaths from RHD from 2000 to 2015. The highest total deaths were reported from Egypt, Pakistan, Iran, Afghanistan, and Yemen, representing 80% of the total death rates for the region (35,248). The highest ASDR was Afghanistan (27.5), followed by Yemen (18.78) and Egypt (15.59). The ASDR for RHD was highest in low income countries. It correlated highly, in all income groups, with anemia during pregnancy. Conclusions: Trends and patterns of deaths from RHD in the EMR have shifted to a later age group and are linked with poverty related to inequalities in development and service delivery for certain age groups and gender.