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Objectives: This study sought to characterize the presentations, electrophysiological features and diagnostic maneuvers for a series of unique arrhythmias involving the HPS., Background: By virtue of its unique anatomy and ion channel composition, the His-Purkinje system (HPS) is prone to a variety of arrhythmic perturbations., Methods: The authors present a collaborative multicenter case series of 6 patients with HPS-related arrhythmias. All patients underwent electrophysiological studies using standard multipolar catheters., Results: In 3 patients, both typical and reverse bundle branch re-entry were seen, with 1 patient demonstrating "figure of 8" re-entry likely involving the septal fascicle. One patient presented with systolic dysfunction associated with a high premature ventricular complex burden, with the mechanism being bundle-to-bundle re-entrant beats masquerading as dual response to a single sinus impulse. Two patients were diagnosed with interfascicular re-entry. Diagnosis was aided by careful assessment of HV interval in sinus rhythm and ventricular tachycardia, multipolar catheters to assess the activation sequence of the His-right bundle branch, and fascicles and entrainment of different components of the HPS. Cure of the arrhythmia was achieved by ablation of the right bundle branch block in 3 patients, the left septal fascicle in 2 patients, and the left posterior fascicle in 1 patient., Conclusions: Proper diagnosis of re-entrant arrhythmias involving the HPS may prove challenging. We emphasize a structured approach for diagnosis and effective therapy., Competing Interests: Author Relationship With Industry The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)