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Objectives: The study aimed at assessing the outcome of pulmonary vein isolation (PVI) using second-generation cryoballoon, Arctic Front Advance, Medtronic (CB-Adv) as a rhythm control strategy for drug-resistant paroxysmal atrial fibrillation (PAF) in a cardiac tertiary care center of Pakistan. Methodology: Fifty patients had PVI with CB-Adv for symptomatic drug-resistant PAF at the National Institute of Cardiovascular Diseases, Karachi, Pakistan, during 2017-2022. Patients were followed-up in the clinic on the 1st, 3rd, and 6th month after the ablation. Twenty-four hours of Holter monitoring of electrocardiogram was obtained on each visit. We conducted a retrospective chart review after approval from the ethical review committee. We collected all the patients' demographic and clinical data, procedural results, and reports of Holter monitoring. The primary outcome was successful PVI and freedom from atrial tachyarrhythmia (Ata) on a 6-month follow-up. Results: We enrolled all 50 patients (34 male, 68%; mean age 55.14 ± 7.94 years) treated with PVI using CB-Adv. The mean duration of symptoms was 30.28 ± 13.48 months. PVI with CBAdv was found to be curative in 49 patients (98%). Following the procedure, pericardial effusion was found in one patient (2%), whereas one patient (2%) had a retroperitoneal hematoma. On a six-month follow-up, only one patient (2%) had a recurrence of Ata, which was PAF. Conclusion: Our experience of PVI with CB-Adv has shown a high success rate of the procedure for rhythm control in patients who have PAF, which is resistant to antiarrhythmic drugs (AADs). [ABSTRACT FROM AUTHOR]