Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated exfoliating skin condition predominated by desquamation and blistering. Neonatal outbreaks have already been reported; however, our outbreak highlights the potential for SSSS following neonatal health promotion measures such as intra-muscular vitamin K administration and metabolic screening (heel prick) as well as effective case containment measures and the value of staff screening. Between February and June 2007, five confirmed cases of neonatal SSSS were identified in full-term neonates born in an Irish regional maternity hospital. All infants were treated successfully. Analysis of contact and environmental screening was undertaken, including family members and healthcare workers. Molecular typing on isolates was carried out. An outbreak control team (OCT) was assembled and took successful prospective steps to prevent further cases. All five Staphylococcus aureus isolates tested positive for exfoliative toxin A, of which two distinct strains were identified on pulsed-field gel electrophoresis analysis. Two cases followed staphylococcal inoculation during preventive measures such as intra-muscular vitamin K administration and metabolic screening (heel prick). None of the neonatal isolates were methicillin resistant. Of 259 hospital staff (70% of staff) screened, 30% were colonised with S. aureus, and 6% were positive for MRSA carriage. This is the first reported outbreak of neonatal SSSS in Ireland. Effective case containment measures and clinical value of OCT is demonstrated. Results of staff screening underlines the need for vigilance and compliance in hand disinfection strategies in maternity hospitals especially during neonatal screening and preventive procedures.