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Numerous studies have reported an association between cytotoxic T-lymphocyte associated antigen 4 gene (CTLA4) polymorphism and susceptibility to asthma, in different populations, but the results have been inconsistent. We performed a meta-analysis of 19 published case–control studies to obtain a reasonably accurate estimation of the relationship between CTLA4 polymorphism and asthma.We searched the Pubmed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases and extracted data from 19 independent, eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) and Egger test were separately used to assess the strength of associations and publication bias.A total of 19 case–control studies involving 4831 cases and 4534 controls were identified. The combined results revealed that there was significant association between the +49A/G polymorphism and asthma (for GG + GA vs. AA: OR = 0.82, 95% CI = 0.70–0.97, P = .02). Stratification by race or age indicated a significant association between the CTLA-4 +49 GA+GG genotype and asthma in Asians (OR = 0.80, 95% CI = 0.68–0.95, P = .01) and children (OR = 0.75, 95% CI = 0.62–0.90, P = .002), but there was no association in whites (OR = 0.94, 95% CI = 0.80–1.10, P = .44) and adults (OR = 0.85, 95% CI = 0.68–1.06, P = .15). Additionally, there was a significant association with atopic asthma under the random-effects model (OR = 0.81, 95% CI = 0.67–0.98, P = .03). In addition, there was no significant association between the −318 C/T polymorphism and asthma risk.Our meta-analysis results suggested that the +49A/G polymorphism in CTLA-4 was an important risk factor for asthma susceptibility, especially in Asian individuals, children, and atopic patients.