Background -This prospective clinical study evaluates the feasibility and eff icacy of combined linear mitral isthmus ablation and pulmonary vein(PV) isolatio n in patients with paroxysmal atrial fibrillation(AF). Methods and Results -One hundred consecutive patients(13 women; age 55±10 years)-with drug-refractory , symptomatic paroxysmal AF underwent PV isolation and linear ablation of the ca votricuspid isthmus and the mitral isthmus(lateral mitral annulus to the left in ferior PV). They were compared with 100 consecutive patients(14 women; age, 52± 10 years) undergoing PV isolation and cavotricuspid ablation without mitral isth mus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating( 1) a parallel corridor of double potentials during coronary sinus(CS) pacing,(2) an activation detour by pacing either side of the line, and(3) differential pac ing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were per formed successfully in all. Mitral isthmus block was achieved in 92 patients aft er 20±10 minutes of endocardial radiofrequency application and an additional 5 ±4 minutes of epicardial radiofrequency application from within the CS in 68, r esulting in a conduction delay of 151±26 ms during CS pacing. Thirty-two patie nts with mitral isthmus ablation compared with 49 without had recurrent atrial a rrhythmia (P=0.02) requiring further ablation. At 1 year after the last procedur e, 87 patients with mitral isthmus ablation and 69 without(P=0.002) were arrhyth mia free without antiarrhythmic drugs, mitral isthmus ablation being the only fa ctor associated with long-term success(RR for AF recurrence, 0.2; CI, 0.1 to 0. 4; P< 0.001). Conclusions -Catheter ablation of the mitral isthmus results cons istently in demonstrable conduction block and is associated with a high cure rat e for paroxysmal AF. Background-This prospective clinical study evaluates the feasibility and eff icacy of combined linear mitral isthmus ablation and pulmonary vein (PV) isolatio n in patients with paroxysmal atrial fibrillation (AF). Methods and Results - One hundred consecutive patients (13 women; age 55 ± 10 years) -with drug-refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation of the ca votricuspid isthmus and the mitral isthmus (lateral mitral annulus to the left in ferior PV). They were compared with 100 consecutive patients (14 women ; age, 52 ± 10 years) undergoing PV isolation and cavotricuspid ablation without mitral isth mus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during coronary sinus (CS) pacing, (2) an activation detour by pacing either side of the line, and (3) differential pac ing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were per formed successfully in all. Mitral i sthmus block was achieved in 92 patients aft er 20 ± 10 minutes of endocardial radiofrequency application and an additional 5 ± 4 minutes of epicardial radiofrequency application from within the CS in 68, esulting in a conduction delay of 151 ± 26 ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared with 49 without had recurrent atrial a rrhythmia (P = 0.02) requiring further ablation. At 1 year after the last procedur e, 87 patients with mitral isthmus ablation and 69 without (P = 0.002) were arrhyth mia free without antiarrhythmic drugs, mitral isthmus ablation being the only fa ctor associated with long-term success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4; P <0.001). Conclusions -Catheter ablation of the mitral isthmus results cons istently in demonstrable conduction block and is associated with a high cure rat e for paroxysmal AF.