Commissural alignment during transcatheter aortic valve implantation (TAVI) has important clinical implications as TAVI expands to younger patients in whom lifetime treatment of aortic valve disease and coronary artery disease is of particular importance. Numerous studies have shown that lack of commissural alignment may adversely affect coronary reaccess and the feasibility of redo-TAVI in this patient population. To assess the risk of commissural misalignment more accurately, we have pioneered and validated the use of a preprocedural imaging protocol that determines valve orientation using multi-detector computed tomography-fluoroscopy co-registration. Furthermore, we have shown that a modified delivery system insertion technique during initial valve deployment results in improved commissural alignment and reduced coronary artery overlap following TAVI with a self-expanding device. However, numerous unanswered questions remain about the impact of commissural misalignment on balloon-expandable valve-in-valve TAVI, especially in patients with unfavorable aortic root anatomy. It is imperative that clinicians consider these anatomic, device-related, and procedure factors, among others, when evaluating patients for transcatheter therapies.