Background— Action potential duration (APD) variation is an important determinant of wave break and reentry. The determinants of APD variability during early ventricular fibrillation (VF) in myopathic human hearts have not been studied. The objective of this study was to study the role of APD restitution and short-term cardiac memory on variation in human VF. Methods and Results— The study consisted of 7 patients (67�9 years old) with ejection fraction <35%. Monophasic action potentials were recorded from the right and/or left ventricular septum during VF. APD _60/90 was measured in sinus beat preceding induction of VF, and its amplitude was used to define 60%/90% repolarization in VF. The monophasic action potential upstroke (dV/dt _max ) was used to characterize local excitability. Simple linear regression showed that variability in APD _n60 was determined by APD/diastolic interval restitution ( R ² =0.48, P <0.0001) and short-term memory (APD ₆₀ n−1, n−2, n−3, n−4; R ² =0.55, 0.40, 0.33, and 0.27 respectively; P <0.001). Using multiple stepwise regression, short-term memory and restitution accounted for 62% of variance in APD ₆₀ ( P <0.001). Individually, memory effect had the greatest contribution to APD variability ( R ² =0.55, P <0.0001). Conclusions— In early human VF, short-term memory and APD/diastolic interval restitution explain most of the APD variability, with memory effects predominating. This suggests that in early human VF, short-term cardiac memory may provide a novel therapeutic target to modulate progression of VF in myopathic patients.