An endoscope seal that effectively inhibits the egress of fluids from the working channel of an endoscope when an elongate device having a non-circular shaft is disposed therein. The endoscope seal includes a body portion having a proximal end adapted for insertion of an elongate device such as a rapid exchange biliary catheter, a distal end adapted for connection to the proximal end of an endoscope, a lumen extending therethrough which is adapted to receive the elongate device and to provide access to the working channel of the endoscope, and a means for conforming to the non-circular shaft of the elongate device to inhibit the flow of fluid from the working channel of the endoscope. The conforming means may, for example, comprise one or more protrusions extending radially inward in the lumen of the body portion, a sealing material such as a surgical foam that is disposed in the lumen of the body portion, or a sealing mandrel. Whether a single protrusion, a plurality of protrusions, a sealing material or a sealing mandrel is utilized, the present invention provides endoscope seals that readily seal about elongate devices having either circular or non-circular profiles.