Background: The advantage of prophylactic cavotricuspid isthmus (CTI) ablation for AF patients without documented atrial flutter is still unclear. The present study aimed to evaluate the role of prophylactic CTI ablation in this population. Methods: A systematic review and meta-analysis study was conducted. The overall effects estimation was conducted using random effects models. The pooled effects were presented as the risk difference and standardised mean difference for dichotomous and continuous outcomes, respectively. Results: A total of 1,476 patients from four studies were included. The risk of atrial tachyarrhythmias following a successful catheter ablation procedure was greater in the pulmonary vein isolation + CTI ablation group than pulmonary vein isolation alone group (34.8% versus 28.2%; risk difference 0.08; 95% CI [0.00–0.17]; p=0.04). Prophylactic CTI ablation was associated with a higher recurrent AF rate (33.8% versus 27.1%; risk difference 0.07; 95% CI [0.01–0.13]; p=0.02). Additional prophylactic CTI ablation to pulmonary vein isolation significantly increased the radio frequency application time (standardised mean difference 0.52; 95% CI [0.04–1.01]; p=0.03). Conclusion: This study suggested that prophylactic CTI ablation was an ineffective and inefficient approach in AF without documented typical atrial flutter patients.