The randomized, controlled trial (RCT) is the cornerstone upon which clinical decision making and practice guidelines are based. RCTs are a crucial step in the scientific progression from bench to bedside, often representing the culmination of important and costly prior investigation. However, with the notable exception of pharmacotherapy for viral hepatitis and inflammatory bowel disease, the fields of gastroenterology and hepatology have been behind the curve in producing RCTs of major clinical impact.