Background. The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, a National Heart, Lung, and Blood Institute-sponsored study in type 2 diabetic patients with coronary artery disease, completed patient recruitment in March 2005. This trial had a nuclear substudy in addition to many other substudies. Methods and Results. After patient enrollment, adenosine gated single photon emission computed tomography perfusion imaging is performed at years 1 and 3. The images are interpreted at the core laboratory. Among the objectives of the nuclear substudy are (1) to determine the impact of the mode of therapy on left ventricular function, extent of ischemia, and scar; (2) to determine the impact of therapy on the progression/ regression of ischemia/scar and changes in left ventricular function between years 1 and 3; and (3) to determine the independent and incremental prognostic value of ischemia, scar, and left ventricular function on the primary and secondary endpoints of the trial in the entire patient population and specified subgroups such as women, elderly patients, and minorities. Conclusions. This article describes the methodology and the initial experience of the nuclear core laboratory in this large multicenter trial and provides a summary of variables that are available for future analysis by the working group. Copyright © 2006 by the American Society of Nuclear Cardiology.