Author's summary Effective ablation approach for persistent atrial fibrillation (PeAF) beyond pulmonary vein (PV) isolation is still controversial. We developed a real-time computational AF modeling technique to perform rapid rotor mapping reflecting the individual electrophysiology and AF mechanisms. In this study, we investigated whether extra-PV ablation targeting a high maximal slope of the action potential duration restitution curve (Smax) improves the outcome of PeAF ablation. However, virtual ablation-guided Smax modulation approach for PeAF did not result in an improved procedural outcome compared to the empirical ablation strategy. Further investigation is needed regarding a more effective patient-customized mechanism-based AF catheter ablation using the functional electrophysiology.