Sphincter of Oddi dysfunction (SOD) can pose diagnostic challenges for the physician. SOD is classified into types I, II, and III, but clinical outcome after sphincterotomy for suspected types II and III SOD has been unpredictable. Therefore, accurate diagnosis of types II and III SOD is important because of the increased risk of sphincterotomy in patients with SOD. Endoscopic sphincter of Oddi manometry (ESOM) is the gold standard for diagnosis of SOD; however, it is associated with significant morbidity and is not an appropriate screening test. Quantitative hepatobiliary scintigraphy (QHBS) has demonstrated good sensitivity as a screening test for SOD in patients following cholecystectomy; however, studies using this methodology are criticized for poor design and patient selection. Recent publications address these criticisms and provide evidence that QHBS and ESOM are comparable diagnostic tools after exclusion of organic biliary obstruction. QHBS can effectively replace invasive ESOM in the diagnostic algorithm of SOD.