In patients with atrial fibrillation, catheter ablation is suggested to reduce the mortality rate and is thus frequently performed. However, peri- and postprocedural thromboembolic complications as well as high recurrence rates of atrial fibrillation limit its advantages and require concomitant anticoagulation. With the advent of novel oral anticoagulants (NOACs), fixed dosing without routine laboratory monitoring became feasible. Nevertheless, several factors are associated with either an overdose or an insufficient drug activity of NOACs. We report on a patient with atrial fibrillation undergoing catheter ablation and cardioversion suffering from ischemic stroke despite being under oral anticoagulation. It turned out that the drug activity of the NOACs used was repeatedly insufficient in spite of regular intake and adequate dosing. In sum, drug activity controls should be taken into consideration in patients with thrombotic events despite oral anticoagulation with NOACs.