OBJECTIVE: To determine costs and effects of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) as compared with standard care (ie, no SDD/SOD (SC)) from a healthcare perspective in Dutch Intensive Care Units (ICUs). DESIGN: A post hoc analysis of a previously performed cluster-randomised trial (NEJM 2009;360:20). SETTING: 13 Dutch ICUs. PARTICIPANTS: Patients with ICU-stay of >48 h that received SDD (n=2045), SOD (n=1904) or SC (n=1990). INTERVENTIONS: SDD or SOD. PRIMARY AND SECONDARY OUTCOME MEASURES: Effects were based on hospital survival, expressed as crude Life Years Gained (cLYG). The incremental cost-effectiveness ratio (ICER) was calculated, with corresponding cost acceptability curves. Sensitivity analyses were performed for discount rates, costs of SDD, SOD and mechanical ventilation. RESULTS: Total costs per patient were euro41 941 for SC (95% CI euro40 184 to euro43 698), euro40 433 for SOD (95% CI euro38 838 to euro42 029) and euro41 183 for SOD (95% CI euro39 408 to euro42 958). SOD and SDD resulted in crude LYG of +0.04 and +0.25, respectively, as compared with SC, implying that both SDD and SOD are dominant (ie, cheaper and more beneficial) over SC. In cost-effectiveness acceptability curves probabilities for cost-effectiveness, compared with standard care, ranged from 89% to 93% for SOD and from 63% to 72% for SDD, for acceptable costs for 1 LYG ranging from euro0 to euro20 000. Sensitivity analysis for mechanical ventilation and discount rates did not change interpretation. Yet, if costs of the topical component of SDD and SOD would increase 40-fold to euro400/day and euro40/day (maximum values based on free market prices in 2012), the estimated ICER as compared with SC for SDD would be euro21 590 per LYG. SOD would remain cost-saving. CONCLUSIONS: SDD and SOD were both effective and cost-saving in Dutch ICUs.