Background: Droperidol increasingly is used as an effective adjunct for conscious sedation during endoscopic procedures. Given the concern for the effects of narcotics and benzodiazepines on sphincter of Oddi motility, and the potential difficulty in sedating patients undergoing sphincter of Oddi manometry, droperidol could be an ideal agent in this setting. Methods: Over a 43-month period, consecutive patients undergoing sphincter of Oddi manometry were studied prospectively. Sphincter of Oddi manometry was performed under general anesthesia in all but 10 patients. Standard retrograde pull-through techniques were used to examine the biliary and/or pancreatic sphincter, depending on the indication for sphincter of Oddi manometry. After the initial two pull-throughs, 5 mg of droperidol were given intravenously and measurements were repeated 5 minutes later. Results: A total of 55 patients were studied (42 women [76%], 13 men; mean age 43 years). The basal biliary sphincter pressures measured in 35 patients before and after droperidol were, respectively, 56 mm Hg and 48 mm Hg (p = 0.02); the basal pancreatic sphincter pressures measured in 22 patients before and after droperidol were, respectively, 92 mm Hg and 67 mm Hg (p = 0.29). By using a definition for sphincter of Oddi dysfunction of a basal pressure greater than 40 mm Hg, droperidol would have resulted in a change in diagnosis in 5 patients undergoing biliary manometry (one misclassified as sphincter of Oddi dysfunction, 4 misclassified as normal), and 6 patients undergoing pancreatic sphincter manometry (5 misclassified as sphincter of Oddi dysfunction, one misclassified as normal) (total 19% of procedures). No complication was associated with droperidol use. Conclusions: Droperidol alters basal sphincter pressures, which in some patients was clinically significant and would have resulted in misclassification. Although safe and well tolerated, droperidol appears to have subtle but clinically significant effects on the sphincter of Oddi.