BACKGROUND The incidence of contrast media reactions administered at the time of ERCP is unknown. Despite the lack of formal recommendations, numerous types of prophylactic regimens are routinely used in patients with a history of prior reactions to intravascular contrast media. OBJECTIVE Our purpose was to document the incidence of contrast media reactions at the time of ERCP and to determine whether various perceived risk factors are predictive of adverse reactions. METHODS Prospective study. METHODS Tertiary academic center. METHODS A total of 601 patients undergoing ERCP as clinically indicated. METHODS ERCP done with full-strength high osmolality contrast media. No prophylactic medications were given to any patient. METHODS Adverse reactions to contrast media. RESULTS Six hundred one patients were enrolled. Eighty patients had prior documented reactions to intravascular contrast media (39 mild, 21 moderate, 20 severe). Of the 80 patients, 15 additionally reported shellfish allergy, and 46 reported allergic diathesis. Of the 521 patients with no prior reaction to intravascular contrast, 215 reported other history of allergic reaction. Forty-nine were allergic to shellfish, and 166 had underlying allergic diathesis. At ERCP, 277 patients had cholangiograms, 48 pancreatograms, and 276 both. The average volume of contrast per ERCP was 22 mL. No adverse reactions associated with the administration of contrast media at the time of ERCP were observed in any of the patients. CONCLUSIONS The incidence of adverse reaction to iodine-containing contrast media administered at the time of ERCP even in patients considered to be at high risk is exceedingly low. The use of prophylactic regimens before ERCP appears to be unnecessary.