BACKGROUND: Recurrent Clostridium difficile infection is a growing problem among children due to both the increasing survival of medically fragile children with complicated chronic medical conditions resulting in prolonged antibiotic exposure and hospitalization and the emergence of strains of Clostridium difficile that are hypervirulent and associated with high rates of relapse. CASE PRESENTATION: This case describes a medically complex 21-month-old Hispanic girl with Pompe disease and B cell immunodeficiency with recurrent Clostridium difficile infection refractory to antimicrobial management. She presented with nine recurrent episodes of Clostridium difficile infection including fever, foul smelling diarrhea, and respiratory distress with failed sustained responses to compliant treatment using metronidazole and pulsed vancomycin therapy. Maternal donor fecal microbiota transplantation was performed with complete symptom resolution and produced a sustained cure, now 5 years in duration. CONCLUSIONS: This patient presented with symptomatic Clostridium difficile at an early age causing significant morbidity and reduced quality of life. After nearly one year of failed medical management, fecal microbiota transplantation provided a cure. Further evidence-based research is necessary to test the safety and efficacy of this low technology, low cost, and morbidity-sparing therapy in children.