OBJECTIVE: The objective of our study was to compare the diagnostic accuracy of IV contrast-enhanced 64-MDCT with and without the use of oral contrast material in diagnosing appendicitis in patients with abdominal pain. MATERIALS AND METHODS: We conducted a randomized trial of a convenience sample of adult patients presenting to an urban academic emergency department with acute nontraumatic abdominal pain and clinical suspicion of appendicitis, diverticulitis, or small-bowel obstruction. Patients were enrolled between 8 am and 11 pm when research assistants were present. Consenting subjects were randomized into one of two groups: Group 1 subjects underwent 64-MDCT performed with oral and IV contrast media and group 2 subjects underwent 64-MDCT performed solely with IV contrast material. Three expert radiologists independently reviewed the CT examinations, evaluating for the presence of appendicitis. Each radiologist interpreted 202 examinations, ensuring that each examination was interpreted by two radiologists. Individual reader performance and a combined interpretation performance of the two readers assigned to each case were calculated. In cases of disagreement, the third reader was asked to deliver a tiebreaker interpretation to be used to calculate the combined reader performance. Final outcome was based on operative, clinical, and follow-up data. We compared radiologic diagnoses with clinical outcomes to calculate the diagnostic accuracy of CT in both groups. RESULTS: Of the 303 patients enrolled, 151 patients (50%) were randomized to group 1 and the remaining 152 (50%) were randomized to group 2. The combined reader performance for the diagnosis of appendicitis in group 1 was a sensitivity of 100% (95% CI, 76.8-100%) and specificity of 97.1% (95% CI, 92.7-99.2%). The performance in group 2 was a sensitivity of 100% (73.5-100%) and specificity of 97.1% (92.9-99.2%). CONCLUSION: Patients presenting with nontraumatic abdominal pain imaged using 64-MDCT with isotropic reformations had similar characteristics for the diagnosis of appendicitis when IV contrast material alone was used and when oral and IV contrast media were used.