ABSTRACTSotalol, a class III antiarrhythmic agent, is used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter (AFIB/AFL). Despite its efficacy, sotalol's use is limited by its potential to cause life‐threatening ventricular arrhythmias due to QT interval prolongation. Traditionally, sotalol administration required hospitalization to monitor these risks. The FDA approval of intravenous (IV) sotalol for loading before oral maintenance aims to reduce hospitalization duration by facilitating an expedited loading dose, transitioning to oral maintenance therapy. This study evaluates the population pharmacokinetics (PK) and pharmacodynamics (PD) of sotalol using data from the Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) Registry, which includes patients with atrial arrhythmias undergoing IV sotalol loading. A nonlinear mixed‐effect modeling approach was used to describe sotalol PK, considering covariates such as age, weight, sex, and renal function. The study also examined the correlation between sotalol plasma concentrations and corrected QT interval (QTc) prolongation. Sotalol PK after IV loading and two oral maintenance doses was adequately described by a two‐compartment model with first‐order elimination in patients with atrial arrhythmias. Weight and creatinine clearance (CrCl) were identified as covariates with significant influence on sotalol PK. A linear regression model adequately described the relationship between QTc and plasma sotalol levels (R2 = 0.27). The Monte Carlo simulations showed that the IV loading doses recommended in the prescribing information did not result in significant prolongation of QTc. The data from this study supports the current dosing recommendations of IV sotalol in patients with AFIB/AFL.