Background COVID-19 pandemic, limiting the availability of anesthesiologists, has impacted heavily on the organization of invasive cardiac procedures such as transcatheter atrial fibrillation (AF) ablation. Objective We compared the safety and efficacy of deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision, against the standard protocol performed with propofol. Methods We retrospectively included all AF ablation procedures performed in 2020: 23 patients sedated with 1% propofol (2 ml bolus followed by infusion starting at 1 mg/Kg/h), 26 patients with dexmedetomidine (infusion starting at 0.7 mcg/Kg/h). Both groups additionally received 1 mcg/Kg of midazolam as a single bolus and 0.05 mg single boluses of fentanyl prior to ablation on each pair of pulmonary veins (PV). Primary outcomes were oxygen desaturation (<90%) or need for assisted ventilation/intubation, bradycardia (heart rate <45 bpm) and persistent hypotension (systolic blood pressure <90 mmHg). Results Baseline characteristics and hemodynamic variables did not differ between the two groups (all p>0.05). In 8/23 (35%) patients propofol infusion velocity reduction was necessary to maintain the hemodynamic values, compared to 7/26 (27%) with dexmedetomidine. Inter-group comparison of hemodynamic variables during the procedure showed no statistically significant difference, despite a trend in favor of dexmedetomidine (3 respiratory depressions and 3 persistent hypotension episodes with propofol vs. 0 with dexmedetomidine; p = 0.057). Conclusion Deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision is safe and effective for AF transcatheter ablation. A trend towards a lower incidence of hypotension and respiratory depression was noted when compared to propofol.