Introduction Cryoballoon ablation (CB) has proven effective to treatment of patients (pts) with atrial fibrillation (AF). However, the isolated efficacy of CB to treat pts with long-standing persistent atrial fibrillation (LSPAF) is less know. We analyzed the acute results and the long-term follow-up of our pts suffering LSPAF and initially treated with CB. Methods A cohort of 44 pts, 37 male (84%) mean age (60±10 year) suffering LSPAF were treated with first (CB1): 15pts, and second (CB2): 29 pts, generation CB. Eight pts (18.1%) had structural heart disease. Prior to CB, all pts were previously electrically cardioverted (CV) and sinus node and A-V nodal function evaluated at electrophysiological study (EP) once in sinus rhythm (SR) before antiarrhythmic drugs (AAD) load. CB ablation procedure was performed after three months waiting period on AAD following CV/EP drug testing. Result CB procedure was performed in 27 (61.4%) in AF, restoring SR in 8 (18.2%). PV isolation (PVI) was achieved in 95.2%. On follow-up of 30±39 months, 16 pts (40%) had AF recurrence. Second procedure (Redo) was performed in 7 pts. After a single procedure, 24 pts (60%) remain in SR without AAD, after Redo, 29 pts (72.5%), and when AAD added, 31 pts (77.5%) remain in SR. Phrenic nerve palsy (PNP) occurred in 9% of pts (75% with CB2). Conclusion CB technique is safe and useful tool to treat pts with LSPAF with 60% success rate maintaining SR without AAD in a long-term follow-up (30±39 months), up to 72.5% after Redo, and to 77.5% when AAD are added. In the majority of pts maintaining SR (77.5%) CB2 was used in 87% of the cases. Patients without structural heart disease along with those who SR was restored during CB showed the best result.