Methicillin-resistant Staphylococcus aureus (MRSA) is still one of major problems of drug-resistant microorganisms and healthcare-acquired infections. Methicillin-resistant Staphylococcus aureus is highly prevalent in patients in neonatal intensive care units (NICU) in Japan. The most predominant MRSA in NICU is multidrug resistant and produces superantigenic exotoxin, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin C (SEC). These predominant MRSA strains belong to coagulase type II, SCCmec type II, mecA-Tn554 polymorph type I-A and show closely related pulse field gel electrophoresis types. The dissemination of MRSA is wide, and there is a pandemic distribution of a single MRSA clone in the NICU of Japan. Since 1992, the nationwide spread of this clone has also led to the development of a new neonatal disease known as neonatal toxic shock-like exanthematous disease (NTED), which is caused by overactivation of vbeta2+ T cells induced by TSST-1. The spread of MRSA in NICU in Japan has been attributed to overcrowding, high rates of extremely low birthweight babies, understaffing, low control measures of infection and overuse of antibiotics. The environment of NICU and infection control intervention should be improved and a new strategy for control like vaccination or probiotics is required.