Background and Aim: Performance of sphincter of Oddi manometry (SOM) at endoscopic retrograde cholangio-pancreatogram (ERCP) is technically demanding and requires that the patient be well sedated. Droperidol is used as an adjunctive agent in patients who are difficult to sedate. Concerns regarding the safety profile of droperidol and its effects on sphincter of Oddi motility has resulted in the search for other potent sedative agents that do not influence SOM readings. Ketamine, a dissociative anesthetic, is increasingly being used as an adjunctive agent for conscious sedation. This study evaluates the effect of ketamine on sphincter of Oddi motility when used as an adjunctive sedative agent during ERCP. Patients and Methods: This is a prospective study of 30 consecutive patients undergoing SOM who were difficult to sedate and required adjunctive ketamine. Manometry was initially performed with intravenous administration of diazepam plus meperidine or a combination of diazepam plus meperidine and midazolam. After the initial two pull-throughs, 20 mg of ketamine was administered intravenously and the measurements were repeated 5 min later. Results: The basal pressures of the biliary sphincter and of the pancreatic sphincter were not significantly altered by ketamine. By using a definition for sphincter of Oddi dysfunction of a basal pressure ≥40 mmHg, concordance (normal vs abnormal) between the basal sphincter pressure before and after ketamine was seen in 28 patients (93%). Ketamine also did not lead to a difference in phasic wave amplitude, duration, or frequency. No complication was associated with ketamine use. Conclusions: Ketamine at 20 mg did not significantly affect SOM parameters. Further studies are required to confirm our preliminary findings before ketamine can be added to the armamentarium of agents used for performance of sphincter of Oddi manometry. © 2007 The Authors.