With the advent of the new novel oral anticoagulants (NOACs) and specifically, their role in patients with atrial fibrillation (AF), the epitaph for warfarin is being written. Leaving aside AF patients with mechanical prosthetic valves or rheumatic mitral stenosis, for whom these agents are not indicated, there hardly seems a role for warfarin in this population any more.  In the aftermath of RE-LY (dabigatran vs warfarin), ROCKET AF (rivaroxaban vs warfarin), ARISTOTLE (apixaban vs warfarin), and ENGAGE AF (edoxaban vs warfarin),  the reports of these pivotal trials taken individually along with the data from multiple meta-analyses examining them together clearly show that better clinical outcomes are obtained with these new agents.  All reduce stroke and systemic embolism at least as well as warfarin; all are superior in reducing hemorrhagic stroke and intracerebral bleeds than warfarin; some are superior to warfarin in reducing all strokes and systemic emboli; and dabigatran is superior at specifically reducing ischemic stroke.  Simultaneously, the NOACs (several or all) have reduced mortality versus warfarin and have reduced major and fatal bleeding versus warfarin. Gastrointestinal bleeding appears higher with the NOACs than warfarin (with the exception of apixaban in the ARISTOTLE trial) but still with lower fatality. None of the NOACs require anticoagulant blood test monitoring (in contrast to warfarin) and all have fewer drug interactions than warfarin.  While rivaroxaban requires significant food intake at the time the dose is taken, none of the NOACs has the multiple food interactions that can plague warfarin users and warfarin dosing.  Additionally, as regards dosing, the options with the NOACs are limited, and infrequently change over time, which contrasts dramatically with the picture seen with warfarin.  Finally, while the medication cost itself of any of the NOACs is higher than that of generic warfarin, multiple cost-effectiveness analyses have shown that when global costs are considered, including factors associated with laboratory testing, care-related costs of strokes, systemic emboli, bleeding, and the like, the NOACs are or may be preferable.  And, in my practice, the higher costs of the NOACs can be lessened by obtaining them through discounted pharmacy sources (such as at COSTCO) and can be offset by purchasing other routine items in discount outlets (again, such as COSTCO) where the significant cost savings on other products purchased can offset higher medication co-pays.