Interventional Cardiology stenting trials historically enrolled patients with only one culprit lesion (1990s) and have progressed to allow enrollment of patients with multiple lesions. Initially for patients with multiple lesions, one target lesion was treated with the study device while another non-target lesion could be treated by standard of care with commercially available devices. In current trials of drug-eluting stents, two, three or more target lesions are being treated with the study device, sometimes in the same coronary artery. This introduces challenges in the design of the trial, collection of the data and analysis of the data. Case studies will be presented and possible methods of analysis will be discussed.