Background and Aims Pancreatic cancer (PC) has a poor prognosis, and etiological evidence regarding potentially modifiable risk factors remains limited. Blood metals are involved in oxidative stress, metabolic regulation, and immune responses, but their causal relationships with PC risk remain unclear. This study aimed to systematically evaluate the potential causal associations between 42 blood metal traits and PC risk using a multi-ancestry Mendelian randomization (MR) framework.Methods Genome-wide association study (GWAS) summary statistics for 42 blood metal traits in East Asian populations were used as exposure data. Two-sample MR analyses were conducted using three PC GWAS datasets, including two East Asian datasets and one European dataset. The inverse-variance weighted (IVW) method was used as the primary analysis, with MR-Egger, weighted median, and weighted mode as complementary approaches. IVW estimates for all 42 metals across the three PC GWAS datasets were subsequently combined using random-effects meta-analysis. Multiple testing was addressed using Bonferroni and Benjamini-Hochberg false discovery rate (FDR) correction. Heterogeneity, horizontal pleiotropy, outliers, leave-one-out analyses, and Steiger directionality testing were performed to assess robustness. MRlap was further used to evaluate the potential impact of sample overlap between the East Asian exposure and outcome GWAS datasets.Results Plasma iron showed directionally consistent positive associations with PC risk across all three PC GWAS datasets and reached nominal statistical significance in each dataset. Random-effects meta-analysis demonstrated that higher genetically predicted plasma iron levels were significantly associated with increased PC risk (pooled OR=1.195, 95% CI=1.089-1.311, P=1.73×10^-4). This association remained significant after Bonferroni correction for 42 comparisons (adjusted P=0.007; FDR-adjusted P=0.007), with no significant between-dataset heterogeneity (I2=0%). Plasma copper showed a nominally significant meta-analytic association and remained significant after FDR correction (FDR-adjusted P=0.042), but not after Bonferroni correction (Bonferroni-adjusted P=0.085). Sensitivity analyses revealed no substantial evidence of directional horizontal pleiotropy, instrumental heterogeneity, outlier-driven effects, or single-variant-driven associations for plasma iron, and Steiger testing supported the direction from plasma iron to PC risk.Conclusion This multi-ancestry, multi-metal MR study provides genetic evidence supporting a potential causal association between higher genetically predicted plasma iron levels and increased PC risk. The association remained robust across outcome datasets and after stringent multiple-testing correction, suggesting that iron homeostasis may contribute to the etiology of PC and warranting further mechanistic and risk-intervention studies.