The etiology of pancreatic cancer (PC) remains poorly understood. High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. The aim of this study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for PC. A case-control study was conducted to examine plasma ferritin levels (n = 1,000 cases; 1,004 controls), two hemochromatosis gene (HFE) SNPs (n = 1,386 cases; 1,386 controls), and PC risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by unconditional logistic regression. We did not observe a significant association between plasma ferritin and PC risk. However, HFE rs1799945 was significantly associated with PC risk, with each additional copy of minor allele T being associated with a 1.21-fold increased risk of PC (OR = 1.21, 95 % CI 1.05-1.39, P = 7.72 × 10(-3)). Overall, high iron levels do not increase the risk of PC. Our observation that HFE rs1799945 increased PC risk warrants replication in additional study populations.