Background The impact of amiodarone on ablation outcome in longstanding persistent atrial fibrillation (LSPAF) patients is not known yet. Objective The purpose of this study was to assess the effect of amiodarone on procedural-outcomes in LSPAF patients undergoing catheter ablation. Methods We enrolled 112 LSPAF patients on amiodarone and scheduled to undergo atrial fibrillation (AF) ablation. Patients were randomized to amiodarone discontinuation 4 months before ablation (group 1, n = 56) and a control group (group 2, n = 56) in which ablation was performed without amiodarone discontinuation. All patients underwent pulmonary vein (PV) antrum and posterior wall isolation, defragmentation and extra PV triggers ablation. Patients were followed up for recurrence for 32 ± 8 months post-ablation. Repeat procedures in all recurrent patients were performed off amiodarone. Results During ablation, AF termination was more frequent in group 2 compared to group 1 [44 (79%) vs 32 (57%), P =.015]. After high-dosage isoproterenol, more non-PV triggers were disclosed in group 1 compared to group 2 (42 [75%] vs 24 [43%] respectively, P <.001). Group 2 had lower procedure, radiofrequency and fluoroscopy times compared to group 1 (2.7 ± 1 vs 3.1 ± 1 h, 69 ± 13 min vs 87 ± 11 min and 64 ± 14 min vs 85 ± 18 min respectively, p <.05). At 32 ± 8 month follow-up, on or off antiarrhythmic drug success rate was 37 (66%) in group 1 and 27 (48%) in group 2 (P =.04). During redo, new non-PV trigger sites were identified in group 2 patients. Conclusion Periprocedural continuous amiodarone was associated with higher organization rate and lower radiofrequency ablation rate. However, masking non-PV triggers increased the late recurrence rate.