A secondary level of prophylaxis has proven to be the most successful in Nepal, a country with an endemic rate of rheumatic heart disease, in combating the severe issues associated with rheumatic heart disease. The use of benzathine penicillin G in secondary prophylaxis of rheumatic heart disease, recommended by several guidelines, has been increasingly abandoned in Nepal due to a lack of national guidelines and the termination of the prior programs. The use of oral penicillin and alternative oral antibiotics, which are less effective in preventing the recurrence of acute rheumatic fever, is on the rise. Nepal urgently needs to develop new national guidelines and ensure their effective implementation in order to slow the increase in the number of rheumatic heart disease patients. In this article, we explore the limitations, challenges, and advantages of using the consensus-supported intramuscular benzathine penicillin G as the first-line drug for the secondary prevention of rheumatic heart disease.