Background Atrial fibrillation (AF) is a frequent cardiac arrhythmia and its treatment frequently requires the use of antiarrhythmic drugs (AAD). AAD therapy is designed to preserve sinus rhythm and regulate heart rate, but it does come with its dangers. To examine the relationship of antiarrhythmic drug therapy with syncope and pacemaker implantation in atrial fibrillation. Methods This study was a retrospective cohort analysis conducted at Hayatabad Medical Complex Peshawar, department of CRC, between 16th, May 2023 to 15th, April 2024. ‘A total of 180 patients diagnosed with atrial fibrillation and treated with antiarrhythmic drugs were included in the study’. Inclusion criteria were patients aged 18 years or older with a diagnosis of atrial fibrillation confirmed by electrocardiography, starting oral antiarrhythmic drug therapy for either rhythm control (amiodarone) or rate control (beta-blockers) and a follow-up period of at least 6 months from the initiation. The study excluded patients with a history of pacemaker implantation or more than trivial structural heart disease and those under treatment for rhythm control of other types of arrhythmias. Demographic data, type of antiarrhythmic drug used, duration of therapy, and clinical outcomes were analyzed. Results The study enrolled 180 patients with atrial fibrillation, ‘with a mean age of 68.5 ± 10.2 years; 112 (62.2%) were males and 68 (37.8%) were females’. The distribution of Body Mass Index was as follows: 10 (5.6%) were underweight, 72 (40.0%) were normal weight, 64 (35.6%) were overweight, and 34 (18.8%) were classified as obese. The ‘logistic regression analysis indicated that the use of Class IC and Class III drugs was associated with a significantly increased risk of syncope, with adjusted odds ratios (ORs) of 2.5 (95% CI; 1.2-5.1, p = 0.01) and 2.1 (95% CI; 1.0-4.4, p = 0.04), respectively’. Conclusion This study highlights that the use of Class IC and Class III antiarrhythmic drugs is associated with syncope as a new factor leading to pacemaker implantation in patients suffering from atrial fibrillation