BACKGROUND: N-acetyl-transferase 2 (NAT2) polymorphisms have been demonstrated to be associated with acute leukemia (AL); however, the results remain controversial. The present meta-analysis was performed to provide more precise results. METHODS: Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were used to identify eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between NAT2 polymorphisms and AL risk. RESULTS: Increased risk was found under both heterozygous (OR 1.24, 95% CI 1.02-1.51) and recessive model (OR 1.28, 95% CI 1.06-1.55) for rs1801280. The slow acetylator phenotype (OR 1.22, 95% CI 1.07-1.40) also increased AL risk. Subgroup analysis demonstrated that rs1801280 increased AL risk under the recessive model (OR 1.14, 95% CI 0.93-1.41) in Caucasian population and the co-dominant (OR 1.77, 95% CI 1.40-2.23), homozygous (OR 3.06, 95% CI 1.88-4.99), dominant (OR 2.22, 95% CI 1.56-3.17), recessive model (OR 2.06, 95% CI 1.35-3.16) in the Mixed populations. Association between rs1799929 and decreased AL risk was found in the co-dominant (OR 0.82, 95% CI 0.70-0.97), homozygous (OR 0.65, 95% CI 0.46-0.93), heterozygous (OR 0.71, 95% CI 0.51-1.00), and the recessive model (OR 0.68, 95% CI 0.49-0.94) in the Caucasian group. As for rs1799931, the same effects were found in the co-dominant (OR 0.68, 95% CI 0.49-0.94) and the dominant model (OR 0.68, 95% CI 0.48-0.97) in the mixed group. CONCLUSION: rs1801280 and the slow acetylator phenotype are risk factors for AL.