Background: Safety, efficacy, and patient comfort are the expectations during pulmonary vein isolation (PVI). We aimed to validate the combined advantages of pre- and periprocedural anticoagulation with non-vitamin K anticoagulants (NOACs) and rigorous left atrial appendage thrombus (LAAT) exclusion with computed tomography (CT). Methods: This study included a population of consecutive patients, between March 2018 and June 2020, who underwent cardiac CT within 24 h before PVI to guide the ablation and rule out LAAT. NOAC was omitted 24 h before the ablation. Results: A total of 187 patients (63% male) underwent CT before PVI. None of the patients experienced stroke during or after the procedure. The complication rate was low, with no thromboembolic events and 2.1% of patients experiencing a major bleeding event. Conclusions: Omitting NOAC 24 h before the ablation might be safe if combined with left atrial thrombus exclusion with computed tomography.