Angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism have long been linked to sporadic Alzheimer disease (SAD), but the established data remained controversial. To clarify this inconsistency, a comprehensive meta-analysis was conducted. Through searching of Pubmed, Embase, Alzgene, China National Knowledge Infrastructure (CNKI) and manually searching relevant references, 53 independent studies from 48 articles were included, involving a total of 8153 cases and 14932 controls. The strength of association was assessed by using odds ratios (ORs) with 95% confidence intervals (CIs). Further stratified analyses and heterogeneity analyses were tested, as was publication bias. Overall, significant associations were revealed between I/D polymorphism and SAD risk using allelic comparison (OR = 1.09, 95%CI = 1.01-1.17, p = 0.030), homozygote comparison (OR = 1.17, 95%CI = 1.01-1.34, p = 0.030) and the dominant model (OR = 1.16, 95%CI = 1.04-1.29, p = 0.008), but they were not sufficiently robust to withstand the false-positive report probability (FPRP) analyses. Otherwise, in subgroup analyses restricted to the high quality studies, the large sample size studies and studies with population-based controls, no significant association was observed in any genetic models. In summary, the current meta-analysis suggested that the ACE I/D polymorphism is unlikely to be a major determining factor in the development of SAD.