This systematic review and individual participant data meta-analysis of randomized controlled trials focuses on the optimal timing for initiating direct oral anticoagulants (DOACs) in patients who have experienced an acute ischemic stroke alongside atrial fibrillation. The study, known as CATALYST, analyzes data from four major trials (TIMING, ELAN, OPTIMAS, and START) to determine if starting DOACs early (within 4 days) significantly reduces the risk of recurrent stroke or hemorrhage. The findings suggest that early DOAC initiation is beneficial in reducing a composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke within 30 days without increasing the risk of bleeding complications. This robust analysis aims to inform clinical practice by providing clearer guidance on anticoagulation timing.