Dual antiplatelet therapy (DAPT) duration in patients undergoing percutaneous coronary intervention (PCI) has long been considered a matter of controversy. Complex-PCI (C-PCI) is considered to be associated with an increased ischemic risk that tends to be greater with progressively higher procedural complexity. Thus, with a view to balance ischemic versus bleeding risks, high complexity of PCI intuitively represents an advocate of prolonged DAPT duration. However, the optimal DAPT strategy in this high ischemic risk subset of patients remains unclear, a fact that is exacerbated by the absence of a universal definition of C-PCI, resulting in a significant between-study heterogeneity. The aim of this review is to highlight the increased risks associated with C-PCI, compare long- versus short-term DAPT regimens regarding safety and efficacy endpoints as well as investigate outcomes in special C-PCI cohorts, such as patients with bifurcation, left main or chronic total occlusion lesions. Furthermore, controversial issues, such as antithrombotic regimens in C-PCI patients with atrial fibrillation, and future perspectives are addressed.