Due to the risk of Shiga-toxin producing Escherichia coli (STEC) transmission, current guidance advises excluding young children from childcare settings until microbiologically clear. Children can shed STEC for a prolonged period, and the cost-effectiveness of exclusion has not been evaluated. Our decision tree analysis, including probabilistic sensitivity analysis, estimated comparative health system costs and effects of exclusion until microbiological clearance versus return to childcare setting before this. Due to the risk of secondary cases, return before microbiological clearance resulted in the incremental loss of 0.019 QALYs, but savings of £156. Using the willingness-to-pay threshold of £20000 per QALY, the incremental net monetary benefit of exclusion until microbiological clearance was £215. Exclusion until microbiological clearance remained cost-effective if the total costs for managing the exclusion were below £576. Return before microbiological clearance may, therefore, become cost-effective in cases where the costs of managing exclusion until microbiological clearance are high and/or the risk of secondary cases is very low. Broadening the decision perspective, including the costs of exclusion to the families, may also impact the recommendation. Further research is needed to assess the risk of STEC transmission from children who have clinically recovered and the impact of STEC and exclusion on families of the affected children.