BACKGROUND Metabolic related nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases around the world. A single nucleotide polymorphism (SNP) rs1501299 (+276G>T) in the adiponectin gene has been recently revealed to be responsible for susceptibility to NAFLD. This meta-analysis intended to assess the association risk of NAFLD and rs1501299 polymorphism. MATERIAL AND METHODS We conducted a literature search on PubMed, Embase, and Cochrane Library databases. All involved studies were selected based on our search criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the strength of the association. Subgroup analysis considered the effects of ethnicity, subject scope, and source of control. Publication bias was assessed by Begg's tests. RESULTS Eight qualified case-control studies with 1639 patients and 1426 controls demonstrated a significant correlation between rs1501299 polymorphism in adiponectin and NAFLD under the dominant model (OR=1.18, 95% CI=1.02-1.36), allelic contrast (OR=1.21, 95% CI=1.09-1.36), homozygote comparison (OR=1.63, 95% CI=1.26-2.01) and the recessive allele model (OR=1.58, 95% CI=1.23-2.02) with evident heterogeneity. No association was observed between the risk of NAFLD and the genotypic variants in heterozygote comparison (OR=1.11, 95% CI=0.95-1.29) without heterogeneity. Subgroup analysis suggested that the sample size could be the potential source of heterogeneity. Source of control was not the reason for between-study heterogeneity and further sensitivity analysis and publication bias revealed good consistency and symmetry in the pooling studies. CONCLUSIONS Results from our current meta-analysis gave insight into the correlation between rs1501299 polymorphism and the risk of NAFLD, indicating the variant of rs1501299 might be related to increased NAFLD susceptibility.