Abstract Background Electrical cardioversion (DCCV) is commonly used for rhythm-control in patients with persistent AF. Use of anti-arrhythmic drugs (AADs) increases rates of acute conversion and longer-term maintenance of sinus rhythm (SR) following DCCV. Of these, Amiodarone is the most effective but has a high side-effect burden. Ranolazine, currently licensed for angina, has been shown to have AF-suppressive effects and works synergistically with Class III AADs. Purpose We aimed to assess outcomes following DCCV in patients treated with a Class III AAD, Ranolazine or in combination at a single UK tertiary Cardiology centre. Methods We retrospectively reviewed DCCV lists from June 2020-February 2022. Patients undergoing DCCV on a Class III AAD (Amiodarone/Dronedarone), Ranolazine or a combination of the two and with documented 1-year follow-up were included. Patients who underwent AF ablation during the follow-up period having remained in SR up to that point were excluded. Acute DCCV success and maintenance of SR at 1-year follow-up were recorded. Results A total of 350 patients underwent DCCV during the study period, of whom 102 (29.1%) were on an AAD. After exclusions, 78 patients were included, as follows: Amiodarone - n=30; Dronedarone - n=23; Ranolazine - n=11; combined Ranolazine + Class III AAD - n=14. Acute outcomes: The proportion of patients achieving SR acutely post-DCCV was as follows: Amiodarone: 27/30 (90.0%) Dronedarone: 21/23 (91.3%) Any Class III AAD: 48/53 (90.6%) Ranolazine: 10/11 (90.9 %) Combined Ranolazine + Class III AAD: 14/14 (100%). 1-year follow-up outcomes (Figure 1): The proportion of patients who had remained in SR at 1 year (mean follow-up 11±1.9 months – similar for all 4 groups) was as follows: Amiodarone: 12/30 (40.0%) Dronedarone: 4/23 (17.4%) Any Class III AAD: 16/53 (30.2%) Ranolazine: 3/11 (27.2%) Combined Ranolazine and Class III AAD: 8/14 (53.3%). Despite including 5 patients (35.3%) who had previously failed an AAD monotherapy, the group taking a combination of Ranolazine and a Class III AAD were numerically more likely to remain in SR at 1-year follow-up than those on Amiodarone or Ranolazine, though neither reached significance. However, combination therapy was significantly more effective than Dronedarone monotherapy (P=0.03) and there was a trend towards improved efficacy compared to any Class III AAD (53.3% vs. 30.2%, P=0.11). There were no significant differences between the 3 monotherapy treatments. Conclusion A combination of Ranolazine and Class III AAD may improve maintenance of SR 1 year post-DCCV compared to a Class III AAD alone. Ranolazine also shows comparable efficacy to traditional Class III agents and could therefore be considered as an alternative for patients in whom a Class III AAD is not desirable. Larger randomised multi-centre trials are warranted to evaluate the efficacy and safety of these treatment strategies.