Rheumatic heart disease (RHD), secondary to group A streptococcal infection is endemic in the developing as well as parts of the developed world with significant costs to the patient, and to the healthcare system. We briefly review the prevalence and cost of RHD in developed and developing nations. We subsequently develop a Markov model to evaluate the cost-effectiveness of three strategies (vs standard no prevention) for preventing RHD in a developing world country: primary prophylaxis (throat swab to detect and subsequently treat group A streptococci as needed); primary prophylaxis (antibiotic prophylaxis for all) with benzathine penicillin G once monthly to all patients (ages 5-21 years) regardless of evidence of infection; and secondary prophylaxis with monthly only to those with echocardiographic evidence of early RHD. Our model suggests that echocardiographic screening and secondary prophylaxis is the best strategy although the strategies change depending on parameters used.