Background— Rapid pulmonary vein (PV) activity has been shown to maintain paroxysmal atrial fibrillation (AF). We evaluated in persistent AF the cycle length (CL) gradient between PVs and the left atrium (LA) in an attempt to identify the subset of patients where PVs play an important role. Methods and Results— Ninety-seven consecutive patients undergoing first ablation for persistent AF were studied. For each PV, the CL of the fastest activation was assessed over 1 minute (PV _fast ) using Lasso recordings. The PV to LA CL gradient was quantified by the ratio of PV _fast to LA appendage (LAA) AF CL. Stepwise ablation terminated AF in 73 patients (75%). In the AF termination group, the PV _fast CL was much shorter than the LAA CL resulting in lower PV _fast /LAA ratios compared with the nontermination group (71±10% versus 92±7%; P <0.001). Within the termination group, PV _fast /LAA ratios were notably lower if AF terminated after PV isolation or limited adjunctive substrate ablation compared with patients who required moderate or extensive ablation (63±6% versus 75±8%; P <0.001). PV _fast /LAA ratio <69% predicted AF termination after PV isolation or limited substrate ablation with 74% positive predictive value and 95% negative predictive value. After a mean follow-up of 29±17 months, freedom from arrhythmia recurrence off-antiarrhythmic drugs was achieved in most patients with PV _fast /LAA ratios <69% as opposed to the remaining population (80% versus 43%; P <0.001). Conclusions— The PV to LA CL gradient may identify the subset of patients in whom persistent AF is likely to terminate after PV isolation or limited substrate ablation and better long-term outcomes are achieved.