To estimate the common effect size of HLA-DRB1 alleles on rheumatoid arthritis (RA) susceptibility across Latin America populations through a meta-analysis combining the results of published data. Case-control studies on HLA-DRB1 association with RA in Latin America were searched up to October 2006. Genotype frequencies were extracted according to both shared epitope (SE) and HLA-DR4 positive or negative alleles. The effect summary odds ratio (OR) and 95% confidence intervals was obtained. Heterogeneity and publication bias were assessed. Eight studies containing 684 cases and 1015 controls were included. Under the random effects model, the common OR was 3.28 (1.93, 5.60) (p<0.0001) and 3.54 (2.47, 5.05) (p=4.22 x 10(-12)) for HLA-DR4 and SE, respectively. There was no evidence of publication bias according to Funnel plot and Egger's regression test (p=0,445 for DR4 and p=0,464 for SE meta-analysis). Significant heterogeneity was observed for HLA-DR4 (I2=81.06%, Q=36.96, p=0.000005) but not for the SE meta-analysis. HLA-DR4 and SE positive HLA-DRB1 alleles (mainly HLA-DRB10404) are associated with RA in Latin Americans. Heterogeneity is expected owing to the diverse degree of admixture between the examined populations. Our findings support the HLA as a major susceptibility locus for RA and validate the SE hypothesis in Latin America.