Atrial fibrillation (AF), the most common of all sustained cardiac arrhythmias, is frequently resistant to antiarrhythmic drugs, and physicians have seen limited success with catheter ablation limited to the right atrium. As a result, the safety and efficacy of systematic biatrial linear ablation for drug resistant AF was investigated. Forty-four patients (54 +/- 7 years) underwent catheter ablation of daily drug-resistant AF. Two right-atrial lines (1 septal and 1 cavotricuspid) and 3-4 left-atrial lines were transseptally performed: 2 joining each superior pulmonary vein to the posterior mitral annulus and 1 interconnecting them. An additional left-atrial septal line from the right superior pulmonary vein (RSPV) to the foramen ovalis was performed in 23 patients. Radiofrequency was delivered with a conventional thermocouple-equipped ablation catheter or with an irrigated tip ablation catheter for resistant cases and for sparing the endocardium. Of the 44 patients, 25 (57%) were successfully treated without antiarrhythmic drugs. Twelve patients (27%) improved (<6 hours of AF per trimester under a previously ineffective drug) and 7 (16%) were considered treatment failures. Multiple sessions were required to ablate new left-atrial macro-reentry and initiating foci (2.7 +/- 1.3 procedures per patient). Five patients had a pericardial effusion and 1 each a pulmonary embolism, an inferior myocardial infarction, and a reversible cerebral ischemic event. One patient had thrombosis of the 2 left pulmonary veins. Despite a relatively high success rate, this procedure is too long, and the safely and efficacy need to be improved and applied to a broader range of patients.