We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents.