The protein tyrosine phosphatase N22 (PTPN22) gene C1858T polymorphism has been reported to be associated with susceptibility to type 1 diabetes (T1D) in relatively small sample sizes. This study aimed at investigating the pooled association by carrying out a meta-analysis on the published studies. The Medline, EBSCO, and BIOSIS databases were searched to identify eligible studies published in English before June 2012. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). The presence of heterogeneity and publication bias was explored by using meta-regression analysis and Begg's test, respectively. A total of 28 studies were involved in this meta-analysis. Across all populations, significant associations were found between the PTPN22 C1858T polymorphism and susceptibility to T1D under genotypic (TT vs. CC [OR = 3.656, 95% CI: 3.139–4.257], CT vs. CC [OR = 1.968, 95% CI: 1.683–2.300]), recessive (OR = 3.147, 95% CI: 2.704–3.663), and dominant models (OR = 1.957, 95% CI: 1.817–2.108). In ethnicity- and sex-stratified analyses, similar associations were found among Caucasians and within Caucasian male and female strata. The meta-analysis results suggest that the PTPN22 C1858T polymorphism was associated with susceptibility to T1D among the Caucasian population, and males who carried the -1858T allele were more susceptible to T1D than females.