In Taiwan, rheumatic fever (RF) and rheumatic heart disease (RHD) remain widespread and constituting a health problem. The long-term prevention of streptococcal infections among rheumatic children has also failed to prevail, and yet has seldom been emphasized. Therefore, recurrence of RF remained prevalent. For an appraisal of the difficulties in the administration of long-term medication prophylaxis, a prospective study was started in 1967. One hundred and five consecutive cases of RF and RHD were followed up for more than 1 year to 6 years with an average of 4.4 years. One hundred and two cases received monthly injections of benzathine penicillin G for 6 months to 6 years, of whom 10 were switched to daily sulfa drugs; 1 case had oral penicillin daily for 6 years; in 12 cases, sulfa drugs were given for 6 months to 5 years. Fifty-one cases (48.6 %) stayed well in the program; 22 (21.0 %) stayed but were not compliant; 32 (30.4 %) dropped out soon or after staying in for more than 1 year. Major risk factors leading to non-compliance are; 1) apparent recovery from the illness or resumption of the normal activity; 2) cram session at school; 3) lack of easy medical care system; and 4) shortage of active participation by the health workers and general practitioners. The present study confirmed that the long-term prevention of streptococcal infection was effective and contributed to the decline of RF recurrence rate from more than 30 % down to 6%. Our study implicates that this important preventive program can not be achieved just only by the hospital staff, but should be approached jointly by all doctors, health and social workers, school teachers and the parents.