The authors prospectively analyzed 1,000 biopsies guided with computed tomography (CT) and performed in 955 patients over a 30-month period. All patients were followed up from 3 months to 2 years. The biopsies were performed in an average of 22 minutes (range, 3-85 minutes) by 26 different radiologists; five radiologists performed 547 of the procedures. Of the 1,000 biopsies, 722 were performed in areas in the liver, retroperitoneum, pancreas, pelvis, and adrenal glands. Of 69 errors in diagnosis, 67 were falsely negative and two were falsely positive; 747 true-positive and 184 true-negative diagnoses were made. CT-directed biopsy for accurate diagnosis was 91.8% sensitive and 98.9% specific, with a positive predictive value of 99.7% and a negative predictive value of 73.3%. Of 11 patients with complications, seven had hematomas, three had pneumothorax, and one had hematuria. No deaths occurred, and only one patient required surgery.