Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it is used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardia (VT), however its ability to suppress recurrent ventricular arrhythmia has not been well examined. In this study, we examined the use of dofetilide for the treatment of PVCs and VT. This was a single-center retrospective cohort study of patients admitted to the University of Michigan between 2015 and 2020 for dofetilide initiation. In patients for whom dofetilide was initiated for PVCs, VT or both, additional descriptive information was collected until date of last clinical follow-up. Successful PVC suppression was defined as 80% reduction in PVC burden compared to pre-dofetilide initiation. A total of 50 patients were admitted for dofetilide initiation for treatment of PVCs (18), VT (27) or both (5). Average left-ventricular ejection fraction was 32.0 +/- 17.2% with 32.7% of patients having ischemic cardiomyopathy and 67.3% of patients having non ischemic cardiomyopathy. A majority (90%) of patients in the cohort had an internal cardioverter defibrillator (ICD). Prior to dofetilide initiation, 40% of patients had undergone ventricular ablations. Previous antiarrhythmic treatments included amiodarone (54.0%), sotalol (28%) and mexilitine (36.0%). Dofetilide was stopped in 8 patients (16%) during index hospitalization for QT prolongation with 3 patients experiencing Torsades de Pointes. In an additional 24 patients, dofetilide was discontinued at a median of 3.3 months for inefficacy (50%) or QT prolongation (50%). Median follow was 36.3 months (range of 3.9 months to 84.8 months). Dofetilide dosing was 500 (35.7%), 250 (45.2%), 125 (19.1%) micrograms. In patients treated for PVCs, PVC frequency decreased from an average of 21.7% to 9.0% (p<.001) with 35.7% of patients meeting criteria for successful suppression. In patients with VT, 80.0% had recurrent ICD shocks after dofetilide (average 1.6 shocks/year of follow-up). 7 patients died over the follow-up period. Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress ICD shocks in a majority of patients and was associated with significant toxicities requiring discontinuation in 40% of patients during the follow-up period.