BACKGROUND AND PURPOSE: Geometrical uncertainties in radiotherapy are generally accounted for by margins for tumors, but their effect on organs-at-risk (OARs) is often ignored. We developed a model that incorporates dose- and geometry-based uncertainties in OAR planning using dose constraints. MATERIALS AND METHODS: Radiotherapy uncertainties cause real dose-volume histograms (DVHs) to spread around the planned DVH. With a RESULTS: Results varied per OAR, fractionation, and constraint-type. If our 2.5mm/3% MD CONCLUSIONS: We introduced a first model relating dose constraints and complication probabilities with treatment uncertainties and safety margins for OARs. Among other things, it quantified how higher constraints can be applied with increasing radiotherapy accuracy.