The aim of the present paper is to evaluate how the use of decision models in the review of portal images can eliminate systematic set-up errors during conformal therapy. Sixteen patients undergoing four-field irradiation of prostate cancer have had daily portal images obtained during the first two treatment weeks and weekly thereafter. The magnitude of random and systematic variations has been calculated by comparison of the portal image with the reference simulator images using the two-dimensional decision model embodied in the Hotelling's evaluation process (HEP). Random day-to-day set-up variation was small in this group of patients. Systematic errors were, however, common. In 15 of 16 patients, one or more errors of >2 mm were diagnosed at some stage during treatment. Sixteen of the 23 errors were between 2 and 4 mm. Although there were examples of oversensitivity of the HEP in three cases, and one instance of undersensitivity, the HEP proved highly sensitive to the small (2−4 mm) systematic errors that must be eliminated during high precision radiotherapy. The HEP has proven valuable in diagnosing very small (<4 mm) errors. When combined with the potential for rapid diagnosis of larger (>4 mm) systematic errors using one-dimensional decision models, HEP can eliminate the majority of systematic errors during the first 2 treatment weeks.