Diagnostic endoscopic retrograde cholangiopancreatography (D-ERCP) is commonly performed for the evaluation of biliary complications after orthotopic liver transplantation (OLT). This practice is contrary to the national trend of reserving endoscopic retrograde cholangiopancreatography (ERCP) for therapeutic purposes. Our aim was to evaluate the clinical yield and complications of D-ERCP in OLT recipients. In this retrospective study, 165 OLT recipients who underwent ERCP between January 2006 and December 2010 at the University of Michigan were divided into 2 groups: (1) a therapeutic endoscopic retrograde cholangiopancreatography (T-ERCP) group (if they met prespecified criteria that suggested a high likelihood of endoscopic intervention) and (2) a D-ERCP group (if there was clinical suspicion of biliary disease but they did not meet any criteria). The 2 groups were compared with respect to the proportion of subjects undergoing high-yield ERCP, which was defined as a procedure resulting in a clinically important intervention that modified the disease course. 66.3% of the D-ERCP procedures were classified as high-yield, whereas 90.1% of the T-ERCP procedures were (P < 0.001). Serious complications were infrequent in both groups. A survey of practitioners caring for OLT recipients suggested that the rate of high-yield D-ERCP seen in this study is congruent with what is considered acceptable in clinical practice. In conclusion, although T-ERCP is more likely to reveal a pathological process requiring an intervention, D-ERCP appears to be an acceptable clinical strategy for OLT recipients because of the high likelihood of a high-yield study and the low rate of serious complications. Liver Transpl, 2012. © 2012 AASLD.