To evaluate the usefulness of pirenzepine for diagnostic double-contrast barium enema study of the large bowel, pirenzepine and scopolamine methyl bromide (SMB) were compared in a single, blind, randomized trial. Sixty consecutive patients were enrolled in the study. Quantitative analysis of bowel distention was done by measuring the maximum diameter of the transverse colon before and after drug administration. Four independent observers blindly evaluated distention and mucosal coating of the large bowel and global quality of the images. No differences were found in the diagnostic performance between the two drugs. However, pirenzepine induced a slight but significantly larger distention of the large bowel (68 ± 12 vs. 65 ± 8 mm, p= 0.02). Heart rate and rhythm during the study were recorded by ECG. SMB induced tachycardia in all patients (from 72 ± 15 to 98 ± 24 beats/min, p < 0.01), whereas pirenzepine did not (from 76 ± 13 to 78 ± 20, p= NS). After SMB, one-patient exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Pirenzepine had a diagnostic performance similar to SMB in avoiding adverse effects elicited by SMB.