The CD33 rs3865444 polymorphism was first identified to be associated with Alzheimer's disease (AD) in European population. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, American, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs3865444 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from previous 27 studies (N = 86,759; 31,106 cases and 55,653 controls) by searching the PubMed, AlzGene, and Google Scholar databases. We identified significant heterogeneity and observed no significant association between the rs3865444 polymorphism and AD in pooled populations (P = 0.264, odds ratio (OR) = 0.97, 95% confidence interval (CI) 0.93-1.02). In subgroup analysis, we identified significant heterogeneity only in East Asian population and observed no significant association between the rs3865444 polymorphism and AD. We further identified significant heterogeneity and observed significant association between the rs3865444 polymorphism and AD in Chinese population. We identified no significant heterogeneity and significant association in North American and European populations. Collectively, our analysis shows that the CD33 rs3865444 polymorphism is associated with AD susceptibility in Chinese, European, and North American populations. We believe that our findings will be very useful for future genetic studies on AD.