Excessive prolongation of cardiac action potential duration (APD) is a risk factor for lethal ventricular arrhythmias. Previously, we have elucidated the underlying mechanisms for the development of early afterdepolarization (EAD)-mediated premature ventricular complexes (PVCs), leading to the occurrence of reentrant ventricular tachycardia in congenital or acquired long QT syndromes. However, a method to prevent EAD-mediated PVC developments has not yet been established. This study aims to theoretically determine the effect of inhibition of the transient outward K⁺ channel current (I_to) on the development of EAD-mediated PVCs. Our previous study (doi:10.1254/jpssuppl.95.0_3-P-226) investigated the relationship between EAD and PVC initiation using a 6 × 6 cm myocardial sheet model consisting of 360,000 human ventricular myocyte model units (Kurata et al., Biophys J, 2005). In the present study, we examined the effect of I_to inhibition on PVC initiation under PVC onset conditions by performing simulations of excitation propagation. Intriguingly, only 10% inhibition of I_to prevented the development of reentrant arrhythmias evoked by EAD-mediated PVCs. Inhibition of I_to by 30% or more completely suppressed EAD developments, resulting in the prevention of PVC initiation. Based on our results, I_to inhibitions may prevent EAD development-mediated reentrant arrhythmias in the long QT syndrome.