Summary Objectives An epidemic of neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) has emerged in Japan. NTED is caused by TSS toxin-1 produced predominantly by methicillin-resistant Staphylococcus aureus (MRSA). Using a large-scale investigation, the present study aimed to elucidate the overall clinical picture of NTED in Japan. Methods We performed nationwide surveys regarding NTED in Japanese neonatal intensive care units (NICUs) in 2000, 2002 and 2005, and summarized the clinical findings of 540 patients. We also performed a case-control study to identify the relationship between patients' clinical findings and NTED. Results The frequency of NTED in Japanese NICUs in 2000 was 52.2% and declined to 28.3% in 2005. The number of NTED patients in 2000 was 240 and decreased to 139 in 2005. In 2005, the isolation of methicillin-sensitive S. aureus (MSSA) increased to 20.0% in term patients. Although no term infants suffered shock or death, preterm patients sometimes developed severe symptoms. Conclusions The number of NTED patients decreased over the 5-year period from 2000 to 2005, even though more than 100 patients contracted NTED in Japanese NICUs in 2005. MSSA as well as MRSA can cause NTED, and NTED is more severe in preterm infants than in term infants.