AIMS Recent observations have raised concerns regarding the activation of the renin-angiotensin system and the development of atrial fibrillation (AF). Some initial studies indicated an association between an angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism and AF, however, the results have been inconsistent. Our aim was to perform a meta-analysis of relevant studies to assess the validity of this association. METHODS AND RESULTS PubMed, Cochrane clinical trials database, and EMBASE were searched through July 2009, and a manual search was also performed. Of the 68 initially identified studies, 18 case-control studies with 7577 patients were finally analysed. No statistically significant associations were found between the ACE I/D polymorphism and AF risk in the genetic additive model and dominant model, whereas a significant association was observed in the recessive model. A significant heterogeneity between individual studies was evident in all three models. Subgroup analyses showed a strong association between the ACE I/D polymorphism and hypertensive AF without significant heterogeneity. CONCLUSION Our meta-analysis suggests that there is insufficient evidence to demonstrate an association between ACE I/D polymorphism and AF risk. However, there seems to be a significant association between ACE I/D gene polymorphic variation and AF in patients with hypertension. Additional studies are warranted to further explore this association in ethnically diverse populations and varied cardiovascular substrates.