Aim: The objective of the present meta-analysis was to investigate whether or not cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) polymorphisms are associated with ankylosing spondylitis (AS) susceptibility. Methods: A systematic search was conducted from the PubMed, ENBASE, and Springer link database up to April 2014. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association between CTLA-4 (+49 A/G) and AS risk. A subgroup analysis based on geographic region and a sensitivity analysis were also conducted. Results: Five studies were eligible for meta-analysis, including 918 cases and 845 controls. The results showed that no significant association was found between AS and CTLA-4 (+49 A/G) for the additive model (G vs. A), dominant model (GG+AG vs. AA), co-dominant model (GG vs. AA, AG vs. AA) and recessive model (GG vs. AG+AA). The OR was 1.09 (95% CI, 0.87-1.38), 1.16 (95% CI, 0.89-1.51), 1.05 (95% CI, 0.75-1.46), 1.15 (95% CI, 0.86-1.52) and 0.99 (95% CI, 0.79-1.23), respectively. Although subgroup analysis demonstrated no association between CTLA-4 (+49 A/G) polymorphisms and susceptibility to AS in Europe and Taiwan, an association was found in Iran through both the co-dominant and dominant models. Exclusion of any individual study did not alter the significance of the final outcome, excepting the result by omitting the study by Huang etal. Conclusions: The present results suggest that the CTLA-4 may not be a major susceptibility locus in humans with AS. The relationship between them may be affected by different geographic populations.