Rheumatic heart disease (RHD) results in morbidity and mortality that is disproportionate among individuals in developing countries compared to those living in economically developed countries. The global burden of disease is uncertain because most previous studies to determine the prevalence of RHD in children relied on clinical screening criteria that lacked the sensitivity to detect most cases. The present study was performed to determine the prevalence of RHD in children and young adults in León, Nicaragua, an area previously thought to have a high prevalence of RHD. This was an observational study of 3,150 children aged 5 to 15 years and 489 adults aged 20 to 35 years randomly selected from urban and rural areas of León. Cardiopulmonary examinations and Doppler echocardiographic studies were performed on all subjects. Doppler echocardiographic diagnosis of RHD was based on predefined consensus criteria that were developed by a working group of the World Health Organization and the National Institutes of Health. The overall prevalence of RHD in children was 48 in 1,000 (95% confidence interval 35 in 1,000 to 60 in 1,000). The prevalence in urban children was 34 in 1,000, and in rural children it was 80 in 1,000. Using more stringent Doppler echocardiographic criteria designed to diagnose definite RHD in adults, the prevalence was 22 in 1,000 (95% confidence interval 8 in 1,000 to 37 in 1,000). In conclusion, the prevalence of RHD among children and adults in this economically disadvantaged population far exceeds previously predicted rates. The findings underscore the potential health and economic burden of acute rheumatic fever and RHD and support the need for more effective measures of prevention, which may include safe, effective, and affordable vaccines to prevent the streptococcal infections that trigger the disease.