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Compliance with secondary antibiotic prophylaxis for acute rheumatic fever (ARF) should decrease the rate of recurrence; however, efficacy in a highly endemic area has not been studied. A retrospective chart review of patients <21 years old with a diagnosis of ARF in the Northern Mariana Islands was performed. Patient compliance with benzathine penicillin G (BPG) prophylaxis was assessed. One hundred forty-four patients with ARF were identified and considered eligible, and the recurrence rate was 38%. Mean level of compliance with BPG was 59% in patients with no recurrence of ARF and 57% in patients with recurrence of ARF. Level of compliance was not shown to be associated with odds of recurrence. There was a trend toward significance (p = 0.06), with those patients who had carditis at the time of diagnosis of ARF having higher odds of recurrence. A remarkably high recurrence rate of ARF was found in this population, but there was no difference in compliance with secondary antibiotic prophylaxis between those with and without recurrence of ARF. These findings stress the need to improve methods of primary prevention and secondary antibiotic prophylaxis for ARF.