The use of anti-ulcer medication in the neonatal intensive care unit (ICU) is common due to the concern for development of catastrophic gastric ulcer disease. In man, however, the use of acid-suppressive medication has been shown in some studies to be a substantial risk factor for the development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and neonatal sepsis. The purpose of the study reported herein is to evaluate the influence of anti-ulcer medications on the development of diarrhoea in the neonatal foal. The use of anti-ulcer medication does not alter the incidence of diarrhoea in foals treated in an ICU. The records of 1710 foals from 6 different equine hospitals were examined and the use of anti-ulcer drugs was recorded. The presence of in-hospital acquired diarrhoea, CDAD, Clostridium perfringens-associated diarrhoea, neonatal sepsis and salmonellosis were documented. In addition, the presence of gastric ulceration, duration of hospital stay and short-term outcome were examined. The use of anti-ulcer medications increased the odds of in-hospital diarrhoea by 2.0 (95% CI 1.4-2.9; P < 0.0001), relative to the use of no anti-ulcer medication. There was no significant association of anti-ulcer medication with CDAD (P = 0.3189) (OR 2.0; 95% CI 0.4-9.5). Further, results indicated that decreased prevalence of gastric ulceration was not associated with use of anti-ulcer drugs among foals in the study for which these data were known (P = 0.5522). Use of anti-ulcer drugs increases the odds of developing diarrhoea, and may not reduce the incidence of gastric ulceration in hospitalised equine neonates. The use of anti-ulcer drugs in neonatal foals being treated in a hospital setting should be carefully evaluated on an individual basis to determine if such use is warranted.