Association studies between Alpha-1-antichymotrypsin (ACT)-17(A>T) polymorphisms and Alzheimer's disease (AD) susceptibility have shown conflicting results. In this investigation, we performed a meta-analysis to assess the purported associations. Subgroup analyses based on ethnicity (Caucasians, East-Asian and American mixed) were also performed including a total of 5,676 AD patients and 5,460 controls for ACT-17. Overall, allele contrast (A vs. T) of ACT -17 polymorphism produced significant results in the worldwide population [Pheterogeneity=0.01, random-effects (RE) odds ratio (OR) 1.12; 95% CI 1.04–1.21, P=0.003] and in the Caucasian population [Pheterogeneity=0.03, RE OR1.11 95% CI 1.01–1.24, P=0.04]. Meta-analyses of other genetic contrasts suggested that the A allele carriers are associated with increased susceptibility to AD in variant populations. No significant association was observed in the East-Asian subgroup analysis. In conclusion, ACT-17 variation presents a risk factor for AD in the worldwide population, especially in the Caucasian population.