PURPOSE: We describe a computerized method of determining target margins for beam aperture design in conformal radiotherapy plans. MATERIALS AND METHODS: The method uses previously measured data from a population of patients to simulate setup error and organ motion in the patient currently being planned. Starting with a clinical target volume (CTV) and nontarget organs from the patient's planning CT scan, the simulation is repeated many times to produce a spatial probability distribution for each organ in the treatment machine coordinate system. This is used to determine a prescribed dose volume (PDV), defined as the volume to receive the prescribed dose, which encompasses the CTV while restricting the volume of nontarget organs within it, according to planner-specified values. The PDV is used to design beam apertures using a conventional margin for beam penumbra. RESULTS: The method is applied to 6-field prostate conformal treatment plans, in which the PDV encloses the prostate and seminal vesicles while limiting the enclosed rectal wall volume. The effect of organ motion is assessed by applying the plans on subsequent CT scans of the same patients, calculating probabilities for tumor control (TCP) and normal tissue complication (NTCP), and comparing with plans designed from a physician-drawn planning target volume (PTV). Although prostate TCP and rectal wall NTCP are found to be similar in the two sets of plans, TCP for the seminal vesicles is significantly higher in the PDV-based plans. CONCLUSIONS: The method can improve the dose conformality of treatment plans by incorporating population-based measurements of treatment uncertainties and consideration of nontarget tissues in the design of nonuniform target margins.