BACKGROUND: The variable loop circular catheter has been shown to be a safe, effective pulsed field ablation catheter for atrial fibrillation treatment. After the commercial launch of the initial waveform (Seq1), a new waveform (Seq230 mL/min) was developed that reduces electrode surface temperature and ablation delivery time (20-3.8 seconds). This study compares the safety and efficacy of Seq1 versus Seq2 across 2 irrigation rates and 2 dosing conditions. METHODS: Twenty-four Yorkshire pigs were treated with pulsed field ablation using the variable loop circular catheter. Subjects were randomized into 3 pulse recipe/irrigation arms (Seq14 mL/min, Seq130 mL/min, and Seq 230 mL/min). Each group was split into a 1× nominal and a 2×-dose group, resulting in 6 total study groups. Animals were monitored for 28±2 days postablation for follow-up remapping procedures before euthanization. Gross necropsy and histopathology were performed on day 28±2. RESULTS: In all groups, 100% acute and chronic pulmonary vein isolation effectiveness was observed, as indicated by transmural, circumferential, pulmonary vein lesions with no evidence of collateral injury. Transmurality in the left atrial appendage, LA roof, and posterior wall was 75% to 100% across all groups and absent at the mitral isthmus. No catheter thrombus/char was observed at Seq230 mL/min or Seq130 mL/min. With Seq14 mL/min, thrombus/char occurred in 25% (1×) and 100% (2×). Hemolysis and myocardial injury marker changes were similar between all groups, with a notable increase in the 2× groups. On echocardiography, Seq230 mL/min microbubbles were rated as few or none, while Seq14 mL/min and Seq130 mL/min were mostly rated moderate or shower. CONCLUSIONS: Consistently durable pulmonary vein isolation was observed across all groups, including Seq14 mL/min, Seq230 mL/min, and Seq130 mL/min across both dosing conditions. Seq230 mL/min was associated with a reduced ablation delivery time (3.8 seconds), zero catheter thrombus formation, and few microbubbles. Higher irrigation flow in Seq130 mL/min also mitigated catheter thrombus formation but did not reduce microbubble generation.