Atrial fibrillation (AF) is a condition that confers increased thromboembolic risk. Oral anticoagulant (OAC) therapy can attenuate this risk. However, use of OAC therapy is determined largely by the presence of additional clinical factors (encapsulated by the CHA2DS2VASc score) that incrementally elevate stroke risk. Currently, there is no specific recommendation regarding urgency of initiation of OAC therapy in the presence of new-onset AF, except where cardioversion is being considered. Recently, it has become increasingly apparent that there is a period immediately following the onset of AF of particularly accentuated thromboembolic risk (with respect to chronic AF): the physiological bases for this risk are as yet incompletely understood. However, given that both inflammation and impaired nitric oxide signaling are pivotally involved in the pathogenesis of AF, these factors may also mediate thrombotic risk in the context of new-onset AF. Advances in OAC therapy have recently been achieved, with development of agents that are comparable or superior to warfarin for mitigation of stroke risk, but with a safety profile similar to aspirin therapy. Thus, the incremental increase in thromboembolic risk experienced by new-onset AF patients constitutes a previously widely neglected case in favor of the rapid application of OAC therapy to such individuals. This review seeks to summarize the thromboembolic risk observed in new-onset AF and the emerging understanding of the physiological bases for this risk.