Theoretical and experimental studies have shown that restitution of the cardiac action potential (AP) duration (APD) plays a major role in predisposing ventricular tachycardia to degenerate to ventricular fibrillation, whereas its role in atrial fibrillation is unclear. We used the Courtemanche human atrial cell model and the Luo-Rudy guinea pig ventricular model to compare the roles of electrical restitution in destabilizing spiral wave reentry in simulated two-dimensional homogeneous atrial and ventricular tissue. Because atrial AP morphology is complex, we also validated the usefulness of effective refractory period (ERP) restitution. ERP restitution correlated best with APD restitution at transmembrane potentials greater than or equal to -62 mV, and its steepness was a reliable predictor of spiral wave phenotype (stable, meandering, hypermeandering, and breakup) in both atrial and ventricular tissue. Spiral breakup or single hypermeandering spirals occurred when the slope of ERP restitution exceeded 1 at short diastolic intervals. Thus ERP restitution, which is easier to measure clinically than APD restitution, is a reliable determinant of spiral wave stability in simulated atrial and ventricular tissue.