Patients with sphincter of Oddi dysfunction have a significantly increased rate of pancreatitis after manometry or sphincterotomy, but septic complications after diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in patients with sphincter of Oddi dysfunction type 2 have not been reported. We describe two patients with sphincter of Oddi dysfunction type 2 in whom Pseudomonas aeruginosa serotype 10 septicemia and multiple small hepatic abscesses developed, all within 48 h after they underwent diagnostic ERCP. The sepsis and hepatic abscesses resolved after successful intravenous antibiotic administration. Despite scrupulous examination of the duodenoscope washing machine and the bottle of water, the bacteria responsible for the sepsis could not be isolated. It is possible that despite disinfection, a nondetectable colony of P. aeruginosa remained in a part of duodenoscope and proliferated to reach a potentially hazardous level the following day. This report highlights the importance administering antibiotic prophylaxis to patients with sphincter Oddi dysfunction type 2 who undergo ERCP, despite the functional nature of the disease.