The aim of this study was to evaluate the discomfort associated with CT colonography compared with colonoscopy and bowel purgation cleansing, and to evaluate patient preference between CT colonography and colonoscopy. In a total of 124 patients, scheduled for multidetector virtual CT colonography and diagnostic colonoscopy, patient acceptance and future preference were assessed during the different steps of the procedure (colon preparation, CT examination, and conventional colonoscopy). Patients who described contradictory findings between the degree of discomfort and their preference regarding follow-up examinations were retrospectively reinterviewed regarding the reason for this discrepancy. Colonoscopy was graded slightly more uncomfortable than virtual CT colonography, but the preparation was clearly the most uncomfortable part of the procedure. Concerning their preference regarding follow-up examinations, 71% of the patients preferred virtual CT colonography, 24% preferred colonoscopy, and 5% had no preference. Twenty-eight percent of the patients preferred virtual CT colonography despite that they thought it was equally or even more uncomfortable than colonoscopy. This was mainly due to the faster procedure (17 patients), the lower physical challenge (14 patients), and the lack of sedation (12 patients) of virtual CT colonography. Factors other than the discomfort related to the examinations play an important role in the patient's preference for virtual CT colonography, namely the faster procedure, the lower physical challenge, and the lack of sedation. Since the preparation plays a major decisive factor in the patient acceptance of virtual CT colonography, more attention should be given to fecal tagging.