Background: Patient-to-patient transmission of methicillin-resisiant Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs) has been well described. We report the first documented outbreak of probable transmission of MRSA from a mother to 3 of her preterm quadruplet infants postnatally. Methods: Routine surveillance of clinical microbiologic laboratory reports revealed an increased incidence of MRSA infections in our NICU, including 3 of 4 preterm quadruplets. Surveillance cultures of the anterior nares of all patients and the quadruplets' parents were performed to detect MRSA carriage. The isolates were typed by pulsed-field gel electrophoresis with the restriction endonuclease SmaI. Infection control strategies included mupirocin treatment and contact isolation precautions for infected/colonized infants. Results: Clinical cultures from infants A. C, and D and surveillance cultures of the quadruplets' mother and 2 additional unrelated infants grew the same clone of MRSA. The mother's only identified risk factors for MRSA acquisition were 2 prepartum hospitalizations related to the multiple gestation and previous treatment with antibiotics. All anterior nares cultures were negative for MRSA after mupirocin treatment. Conclusions. Use of gowns and gloves by the family members of women with multiple gestations should be recommended to prevent transmission of potential pathogens in the NICU.