The CCS AF guidelines recommendation of using a NOAC over warfarin for most patients with NVAF requiring OAC was predominantly on the basis of data that compared NOACs with warfarin in RCTs. As experience with these agents in clinical practice outside carefully-controlled RCTs has increased, published observational data add support to the current CCS recommendation. Observations from large government, insurance, and health system databases, including that of the US Food and Drug Administration Minisentinel database, show that, in widespread clinical use, NOACs are associated with effects on stroke and bleeding consistent with RCT data. It is important to note that in some publications, only bleeding event data are provided, without corresponding stroke prevention results. Although these “real world” data are nonrandomized and come with limitations common to administrative databases, consistency with RCT findings provides reassurance regarding the safety of NOACs in general clinical care.