Ireland reports the highest incidence of verotoxigenic Escherichia coli (VTEC) infection in Europe. This study investigated potential risk factors for confirmed sporadic and outbreak primary VTEC infections during 2008-2013. Overall, 989 VTEC infections including 521 serogroup O157 and 233 serogroup O26 were geo-referenced to 931 of 18 488 census enumeration areas. The geographical distribution of human population, livestock, unregulated groundwater sources, domestic wastewater treatment systems (DWWTS) and a deprivation index were examined relative to notification of VTEC events in 524 of 6242 rural areas. Multivariate modelling identified three spatially derived variables associated with VTEC notification: private well usage [odds ratio (OR) 6∑896, P < 0∑001], cattle density (OR 1∑002, P < 0∑001) and DWWTS density (OR 0∑978, P = 0∑002). Private well usage (OR 18∑727, P < 0∑001) and cattle density (OR 1∑001, P = 0∑007) were both associated with VTEC O157 infection, while DWWTS density (OR 0∑987, P = 0∑028) was significant within the VTEC O26 model. Findings indicate that VTEC infection in the Republic of Ireland is particularly associated with rural areas, which are associated with a ubiquity of pathogen sources (cattle) and pathways (unregulated groundwater supplies).