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Aims Ablation of outflow tract ventricular arrhythmias may be limited by a deep intramural location of the arrhythmogenic source. This study evaluates the acute and long-term outcomes of patients undergoing ablation of intramural outflow tract premature ventricular complexes (PVCs). Methods and results This multicenter series included patients with structurally normal heart or nonischemic cardiomyopathy and intramural outflow tract PVCs defined by: (a) ≥ 2 of the following criteria: (1) earliest endocardial or epicardial activation < 20ms pre-QRS; (2) Similar activation in different chambers; (3) no/transient PVC suppression with ablation at earliest endocardial/epicardial site; or (b) earliest ventricular activation recorded in a septal coronary vein. Ninety-two patients were included, with a mean PVC burden of 21.5±10.9%. Twenty-six patients had had previous ablations. All PVCs had inferior axis, with LBBB pattern in 68%. In 29 patients (32%) direct mapping of the intramural septum was performed using an insulated wire or multielectrode catheter, and in 13 of these cases the earliest activation was recorded within a septal vein. Most patients required special ablation techniques (one or more), including sequential unipolar ablation in 73%, low-ionic irrigation in 26%, bipolar ablation in 15% and ethanol ablation in 1%. Acute PVC suppression was achieved in 75% of patients. Following the procedure, the PVC burden was reduced to 5.8±8.4%. The mean follow-up was 15±14 months and 16 patients underwent a repeat ablation. Conclusion Ablation of intramural PVCs is challenging; acute arrhythmia elimination is achieved in 3/4 patients, and non-conventional approaches are often necessary for success.