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Objectives: The authors report their experience of a protocol for deep sedation with ketamine in spontaneous respiration during the pulsed-field ablation (PFA) of atrial fibrillation (AF)., Design: Observational, prospective, nonrandomized fashion., Setting: Single-center hospitalized patients., Participants: All consecutive patients undergoing PFA of AF., Interventions: Patients undergoing deep sedation with intravenous ketamine., Measurements and Main Results: The authors' sedation protocol involves the intravenous administration of fentanyl (1.5 µg/kg) and midazolam (2 mg) at low doses before local anesthesia with lidocaine. A ketamine adjunct (1 mg/kg) in 5-minute boluses was injected about 5 minutes before the first PFA delivery. The authors enrolled 117 patients (age = 59 ± 10 y, 74.4% males, body mass index = 27.6 ± 5 kg/m 2 , fluoroscopy time = 24 ± 14 minutes, skin-to-skin time = 80 ± 40 minutes and PFA LA dwell time = 24 ± 7 minutes). By the end of the procedure, pulmonary vein isolation had been achieved in all patients using PFA alone. The mean time under sedation was 54.9 ± 6 minutes, with 92 patients (79%) being sedated for <1 hour. A satisfactory Ramsay Sedation Scale level before ketamine administration was achieved in all patients, except one (80.3% of the patients with rank 3; 18.4% with rank 2). In all procedures, the satisfaction level was found acceptable by both the patient and the primary operator (satisfactory in 98.2% of cases). All patients achieved a Numeric Rating Scale for Pain ≤3 (none or mild). No major procedure or anesthesia-related complications were reported., Conclusion: The authors' standardized sedation protocol with the administration of drugs with rapid onset and pharmacologic offset at low doses was safe and effective, with an optimal degree of patient and operator satisfaction., Competing Interests: Declaration of Competing Interest M. Malacrida is an employee of Boston Scientific. The other authors have no conflicts of interest to declare that they are relevant to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)