The association between cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) exon-1 +49 A/G polymorphism and Hashimoto's thyroiditis (HT) has been widely studied. The results, however, are mixed. This study provides a comprehensive evaluation of the relationship between the genetic risks of CTLA-4 +49 A/G polymorphism and HT. A meta-analysis was conducted in over 4,600 subjects included in 18 case-control studies that were published up to November 15th, 2012. Our meta-analysis indicated that the CTLA-4 genotype was associated with the risk of HT in the allele comparison, homozygote comparison, heterozygote comparison, the dominant genetic model and the recessive genetic model. In the dominant genetic model, variant G allele carriers (GG + GA) of CTLA-4 +49 A/G polymorphism increased the risk of HT comparing to the homozygote AA [odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.37-2.12 for GG + AG vs. AA]. The analysis by ethnicity groups suggested that Asian population (OR = 2.13, 95% CI 1.48-3.07 for GG + AG vs. AA) and Caucasian population (OR = 1.47, 95% CI 1.13-1.91 for GG + AG vs. AA) had significant increased HT risks. The association remained significant after adjusting for publication bias using the trim and fill method. Sensitivity analysis showed that the results were less stable, suggesting that these results should be explained with caution. In summary, this meta-analysis suggested that CTLA-4 +49 A/G polymorphism may be a risk factor for HT.