Background-Atrial stretch causes remodeling that predisposes to atrial fibrillation. We tested the hypothesis that peaks in left atrial (LA) wall stress are associated with focal remodeling. Methods and Results-Nineteen patients underwent LA mapping before catheter ablation for persistent atrial fibrillation.Finite Element Analysis was used to predict wall stress distribution based on LA geometry from CT. The relationship was assessed between wall stress and (1) electrogram voltage and (2) complex fractionated atrial electrograms (CFAE), using CFAE mean (the mean interval between deflections). Wall stress varied widely within atria and between subjects (median, 36 kPa; interquartile range, 26 -51 kP). Peaks in wall stress (Ն90th percentile) were common at the pulmonary vein (PV) ostia (93%), the appendage ridge (100%), the high posterior wall (84%), and the anterior wall and septal regions (42-84%). Electrogram voltage showed an inverse relationship across quartiles for wall stress (19% difference across quartiles, Pϭ0.016). There was no effect on CFAE mean across quartiles of wall stress. Receiver operating characteristic analysis showed high wall stress was associated with low voltage (ie, Ͻ0.5 mV) and electrical scar (ie, Ͻ0.05 mV; both PϽ0.0001) and with absence of CFAE (ie, CFAE mean Ͻ120 ms; PϽ0.0001). However, peaks in wall stress and CFAE were found at 88% of PV ostia. Conclusions-Peaks in wall stress were associated with areas of low voltage, suggestive of focal remodeling. Although peaks in wall stress were not associated with LA CFAE, the PV ostia may respond differently. (Circ Arrhythm Electrophysiol. 2012;5:351-360.)