Background: The class III antiarrhythmic sotalol is renally eliminated with a dose-related propensity to cause adverse drug reactions (ADR) potentially leading to life-threatening arrhythmias. Although product labeling recommends once daily dosing in patients with renal impairment, twice daily dosing is commonly utilized. This study evaluates the safety of this practice. Methods: This retrospective, observational study examined renally impaired patients with atrial fibrillation or atrial flutter admitted for sotalol initiation from July 1, 2012 - December 31, 2014, then for up to 20 months after initiation. Primary endpoints included rates of ADR and therapy changes due to ADR. Secondary endpoints included therapy changes due to arrhythmia recurrence, admissions due to arrhythmia recurrence, and therapy changes for any cause. Results: Analysis included 134 patients with an average creatinine clearance of 51 ml/min, followed over a median of 170 days. Length of stay averaged 3 days with ADR occurring in 53.7% of patients, most commonly QT prolongation or bradycardia. Therapy change due to ADR occurred in 45.5% of patients (n=61). Therapy change due to arrhythmia recurrence occurred in 23.1% (n=31), admission due to arrhythmia recurrence occurred in 24.6% (n=33), and therapy change for any cause occurred in 74.6% (n=100). Conclusion: Initiating sotalol twice daily in renally impaired patients results in ADR and therapy change rates consistent with rates seen in clinical practice for non-renally impaired patients, with minimal length of stay. This practice may be reasonable when initiated in the acute care setting with subsequent outpatient monitoring, however further study is needed.