Erythromycin is a known prokinetic (cholecystokinetic) drug. Recently, erythromycin has been linked to the occurrence of arrhythmias and cardiac death due to QT prolongation. Azithromycin is similar to erythromycin in structure, but has the least arrythmogenic tendency among all the macrolides. This study was aimed at determining the comparative cholecystokinetic effects of erythromycin and azithromycin. Twenty four apparently healthy males were studied in pre-prandial and postprandial states. Thirty minutes before the study (after an overnight fast), the subjects took 500 mg azithromycin and erythromycin in a randomized cross over method. Immediately before the ingestion of a standardized liquid meal, the length, width and height of the gallbladder was measured in each subject to obtain the ellipsoid volume using real time sonography and in supine position. After the ingestion of the liquid meal, the gallbladder measurements were obtained every 5 min for 40 min. The gallbladder contraction index (GBCI) was calculated for each period as a percentage change in volume using the fasting volume as the initial volume in all the calculations. The weight, height and age of each subject were obtained. Statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) software; paired t-tests were used to compare GBCI values in erythromycin and azithromycin interventions. P<0.05 was the criterion for statistical significance. In majority of the periods, erythromycin showed significantly higher GBCI values than azithromycin; azithromycin showed higher GBCI values in few points. Erythromycin has cholecystokinetic superiority over azithromycin. From tolerance point of view, azithromycin should be the preferred drug as it does not have significant drug-drug interaction and may be a potential new treatment of cholestasis. Key words: Sonography, erythromycin, azithromycin, gallbladder motility, cholecystokinesis.