Prophylactic antibiotics are used in an attempt to avoid the septic complications of endoscopic retrograde cholangiopancreatography (ERCP). We prospectively performed blood cultures and surveyed patients for complications. The aims were first, to determine the incidence of bacteraemia associated with ERCP, second, to assess the incidence of clinical sepsis following the procedure and third, to evaluate the effectiveness of our antibiotic prophylaxis. One hundred and fifty successive patients underwent 179 ERCP. Bacteraemia related to the procedure or the underlying pathology was found in nine procedures (5.2%). Bacteraemias were more likely to complicate therapeutic procedures (P = 0.015), biliary obstruction (P = 0.045) or underlying pathology (P = 0.022). Although 61% of ERCP received antibiotics, 22 septic events occurred. Five bacteraemic patients were septic despite antibiotics. Septic complications were associated with the same factors as bacteraemia. It was concluded that patients with biliary obstruction and undergoing therapeutic endoscopic procedures are at greatest risk of bacteraemia. Single dose prophylactic antibiotics may not prevent sepsis in these patients and longer-acting drugs or repeated dosing may be necessary.