Background: Catheter ablation of atrial fibrillation is recommended for patients with symptomatic paroxysmal atrial fibrillation (PAF) despite anti-arrhythmic drugs (AADs). Radiofrequency ablation is widely accepted as an effective treatment for PAF. Cryoenergy by cryoballoon technique is an alternative to radiofrequency (RF) ablation. Cryoballoon ablation is safe, and has a similar success rate in comparison to RF ablation. AF recurrence with cryoballoon ablation is roughly 30%. The aim of this study is to determine the predictors of AF recurrence after cryoballoon ablation.Methods and Results: Sixty one patients with symptomatic PAF despite AADs without structural heart disease were included. Cryoballoon ablation was performed in 60 patients (36 males, mean age: 54.6 +/- 10.7, mean left atrium size: 3.74 +/- 0.39 mm). Transthoracic echocardiography including tissue Doppler imaging was performed in all subjects during sinus rhythm at baseline and after the ablation. Intra-atrial and inter-atrial electromechanical delays, and PA-lateral were measured. All patients were scheduled for 24 h Holter recording at baseline and at 3, 6, 9 months follow-up. Venous samples were collected to measure CK-MB, Troponin-T (TnT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels at baseline and 24 h after ablation. Median follow up was 10 (8-12) months. Forty eight (80%) patients were in sinus rhythm during the follow up. In receiver operating curve (ROC) analysis, intraleft atrial electromechanical delay and PA-lateral achieve an area under the curve (AUC) 0.97 (p < 0.001) and 0.69 (p < 0.001) for the ability to predict AF recurrence. A cut-off value for baseline intraleft atrial electromechanical delay of 29.5 ms predicted AF recurrence with sensitivity of 85% and specifity of 98%. A cut-off value for PA-lateral of 125 ms predicted AF recurrence with sensitivity of 80% and specifity of 90%. In ROC analysis, age achieves an AUC 0.822 (p = 0.006) for the ability to predict AF recurrence. A cut-off value for age of 64 predicted AF recurrence with sensitivity of 71% and specifity of 90%. Early recurrence of AF (HR = 60, 95% CI 18.61-417.86, p < 0.001) predicted also late recurrence of AF.Conclusions: The increase in AF recurrence by increased intraleft atrial electromechanical delay, PA-lateral and older age show the importance of substrate in AF mechanism. Early recurrence was the strongest predictor of late recurrence of AF; therefore, existence of blanking period for cryoballoon ablation should be questioned.