Determining if a medication is effective should be easy: Either the condition is or is not improved. However, the truth is often more complex than that, including in the antiarrhythmic drug (AAD) management of atrial fibrillation. In clinical trials, AAD efficacy is usually determined by the time to first atrial fibrillation recurrence. Another AAD efficacy endpoint, in patients with cardiac implantable electrical devices, is a reduction of atrial fibrillation burden. Other cardiovascular outcomes have included hospitalization, heart failure, and cardiovascular or total mortality. In clinical practice AADs, for atrial fibrillation, are prescribed to reduce symptoms/improve quality of life, which usually correlate with reduced atrial fibrillation frequency, duration, and beneficial hemodynamic effects in certain patient subgroups. Time to first recurrence is not a reliable predictor of clinical efficacy endpoints in practice. This article presents a review for the practitioner of AAD efficacy endpoints in clinical trials versus those in clinical practice and why such differences are present.