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Background and Objective: MicroRNA (miR)-499 rs3746444 polymorphisms may participate in the pathogenesis of autoimmune diseases, but the results remain conflicting. We further investigated this association using a meta-analysis., Methods: We conducted a retrieval of studies and obtained the eligible studies if they met inclusion criteria. Two researchers independently extracted the data from original articles. The genotype frequencies were analysed using Stata software., Results: We finally archived six eligible studies that included 1,118 cases and 1,673 controls. After pooling the data, the results indicated that homozygote TT had an overall association with autoimmune diseases (TC + CC vs. TT: odds ratio [OR] 1.31, 95% CI 1.11-1.55, p = 0.001). The allele C, genotype TC and CC, may be associated with rheumatoid arthritis (RA) risks in Mediterranean populations (C vs. T: OR 2. 00, 95% CI 1.37-2.91, p < 0.001; TC vs. CC + TT: OR 1.76, 95% CI 1.27-2.44; p = 0.001; CC vs. TC + TT: OR 2.31, 95% CI 1.24-4.27, p = 0.008; CC vs. TT: OR 2.92, 95% CI 1.59-5.37, p = 0.001; TC vs. TT: OR 1.98, 95% CI 1.42-2.77). The genotype TT may decrease the risk of RA in Mediterranean populations (TC + CC vs. TT: OR 2.15, 95% CI 1.57-2.94, p < 0.001) rather than in East Asians., Conclusions: This study suggested that miR-499 polymorphisms were associated with a significantly increased risk of RA in Mediterranean populations.