The goal of this study was to report a multicenter series of left-sided catheter ablations performed by using intravenous direct thrombin inhibitors (DTIs) as an alternative to heparin.Amidst a looming worldwide shortage of heparin, there are insufficient data to guide nonheparin-based peri-procedural anticoagulation in patients undergoing catheter ablation.This study reviewed all catheter ablations at 6 institutions between 2006 and 2019 to assess the safety and efficacy of DTIs for left-sided radiofrequency catheter ablation of atrial fibrillation and ventricular tachycardia.In total, 53 patients (age 63.0 ± 9.3 years, 68% male, CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score 2.8 ± 1.6, left ventricular ejection fraction 46 ± 15%) underwent ablation with DTIs (75% bivalirudin, 25% argatroban) due to heparin contraindication(s) (72% heparin-induced thrombocytopenia, 21% heparin allergy, 4% protamine reaction, and 4% religious reasons). The patient's usual oral anticoagulant was continued without interruption in 69%. Procedures were performed for atrial fibrillation (64%) or ventricular tachycardia/premature ventricular contractions (36%). Transseptal puncture was undertaken in 81%, and a contact force-sensing catheter was used in 70%. Vascular ultrasound was used in 71%, and femoral arterial access was gained in 36%. A bolus followed by infusion was used in all but 4 cases, and activated clotting time was monitored peri-procedurally in 72%, with 32% receiving additional boluses. Procedure duration was 216 ± 116 min, and ablation time was 51 ± 22 min. No major bleeding or embolic complications were observed. Four patients had minor self-limiting bleeding complications, including a small pericardial effusion (<1 cm), a small groin hematoma, and hematuria.In this multicenter series, intravenous DTIs were safely used as an alternative to heparin for left-sided catheter ablation.