Background: Mechanical stretch and oxidative stress have been shown to prolong action potential duration (APD) and produce early-afterdepolarizations (EADs). Here, we developed a simulation model to study the role of stretch-activated-channel (SAC) currents in triggering EADs in ventricular myocytes under oxidative stress. Methods and Results: We adapted our coupling clamp circuit so that a model ionic current representing the actual SAC current was injected into ventricular myocytes and added as a real-time current. This current was calculated as I_SAC=G_SAC*(V_m-E_SAC), where G_SAC is the stretch activated conductance, Vm is the membrane potential and E_SAC is the reversal potential. In rat ventricular myocytes, application of G_SAC did not produce sustained automaticity or EADs, although turn-on of G_SAC did produce some transient automaticity at high levels of G_SAC. Exposure of myocytes to 100µM H₂O₂ induced significant APD prolongation and increase in intracellular Ca²⁺ load and transient, but no EAD or sustained automaticity was generated in the absence of G_SAC. However, the combination of G_SAC and H2O2 consistently produced EADs at lower levels of G_SAC (2.6±0.4 nS, n=14, p<0.05). Pacing myocytes at a faster rate further prolonged action potential duration and promoted the development of EADs. Conclusions: SAC activation plays an important role in facilitating the development of EADs in ventricular myocytes under acute oxidative stress. This mechanism may contribute to the increased propensity to lethal ventricular arrhythmias seen in cardiomyopathies where the myocardium stretch and oxidative stress are generally co-exist.