Background: Neonatal diarrhoea is a frequent clinical condition in commercial swine herds, previously regarded to be uncomplicated to treat. However, since 2008 it seems that a new neonatal diarrhoeic syndrome unresponsive to antibiotics and common management practices has emerged. Routine laboratory examinations have not detected any pathogen related to this syndrome. The primary purpose of this study was to evaluate if well-known enteric pathogens could be associated with outbreaks of neonatal diarrhoea, thus question the hypotheses of a new syndrome. Furthermore, we wanted to evaluate macroscopic and microscopic findings associated with these outbreaks and if possible propose a preliminary piglet-level case-definition on syndrome New Neonatal Porcine Diarrhoea syndrome (NNPDS). Results: Four well-managed herds experiencing neonatal diarrhoea with no previously established laboratory conclusion and suspected to suffer from New Neonatal Porcine Diarrhoea Syndrome, were selected. Within these herds, 51 diarrhoeic and 50 non-diarrhoeic piglets at the age of three to seven days were necropsied and subjected to histological and microbiological examination. Faeces were non-haemorrhagic. Neither enterotoxigenic E. coli, Clostridium perfringens type A or C, Clostridium difficile, rotavirus, coronavirus, Cryptosporidium spp, Giardia spp, Cystoisospora suis nor Strongyloides ransomi were associated with diarrhoea in the investigated outbreaks. Macroscopically, the diarrhoeic piglets were characterized by filled stomachs and flaccid intestines without mucosal changes. The predominant histological lesions were villous atrophy in jejunum and ileum. Epithelial lesions in colon were seen in one third of the case piglets. Conclusions: The results of the study supported the hypothesis that a new neonatal porcine diarrhoea was present in the investigated herds, since no known pathogen(s) or management factors could explain the diarrhoeal outbreaks. Based on the findings in the four herds the following case-definition of NNPDS was suggested: Non-haemorrhagic diarrhoea during the first week of life, without detection of known infectious pathogens, characterized by milk-filled stomachs and flaccid intestines at necropsy.