The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg’s test, and Egger’s test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05–1.12), 1.17 (1.12–1.23), 1.26 (1.18–1.36), 1.17 (1.10–1.24), 1.30 (1.17–1.44), and 1.25 (1.11–1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose–response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.