The child day-care centre (DCC) is often considered as one risk factor for gastroenteritis (GE) rather than a complex setting in which the interplay of many factors may influence the epidemiology of GE. This study aimed to identify DCC-level risk factors for GE and major enteropathogen occurrence. A dynamic network of 100 and 43 DCCs participated in a syndromic and microbiological surveillance during 2010–2013. The weekly incidence of GE events and weekly prevalence of five major enteropathogens (rotavirus, norovirus, astrovirus, Giardia lamblia, Cryptosporidium hominis/parvum) were modelled per DCC using mixed-effects negative binomial/Poisson regression models. Sixteen hundred children were surveyed up to 3 years, during which 1829 GE episodes were reported and 5197 faecal samples were analysed. Identified risk factors were: large DCC capacity, crowding, having animals, nappy changing areas, sandpits, paddling pools, cleaning potties in normal sinks, cleaning vomit with paper towels (but without cleaner), mixing of staff between child groups, and staff members with multiple daily duties. Protective factors were: disinfecting fomites with chlorine, cleaning vomit with paper towels (and cleaner), daily cleaning of bed linen/toys, cohorting and exclusion policies for ill children and staff. Targeting these factors may reduce the burden of DCC-related GE.