Background Acute ischemic stroke (AIS) in patients with non-valvular atrial fibrillation (AF) despite oral anticoagulation (OAC) is a complex and insufficiently investigated setting. Potential strategies range from maintaining the current OAC to changing the substance class. We have queried the specific treatment standards on German stroke units (SUs). Methods By means of a standardized online questionnaire via SurveyMonkey™ (San Mateo, CA, USA), all clinical heads of German SUs were asked about their treatment standards in the following clinical situations: first AIS of an OAC-naïve AF patient, AF patient with AIS despite administration of a vitamin K antagonist (VKA), AF patient with AIS despite administration of direct OAC (DOAC). In addition, the performance of specific coagulation tests in AF patients with AIS despite OAC was queried. Results 160 (48%) clinical heads of German SU responded. Data from pivotal trials (84%), own experience with substances (71%), and side-effect profiles (66%) determine the initial DOAC prescription. In case of an AIS despite OAC, 83 and 18% would switch from VKA to DOAC under certain conditions and always, respectively. Half of respondents would switch from DOAC to VKA under certain conditions, while the other half would decline. 96% would switch to an alternative DOAC. The vast majority of those who made preconditions considered concomitant diseases (92, 90, and 81%, respectively). Few would consider infarct pattern (<35%). 61% perform initial coagulation tests (only one-third substance-specific assessments); however, the majority do not use these to make further decisions. Conclusions In the setting of an OAC-naïve AF patient with AIS, established pivotal data are most respected. In the unclear setting of an AIS despite OAC, most respondents consider concomitant diseases and give preference to switching to a (different) DOAC.