Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species and plays an important role in the aetiology of cancer. The MPO -463G>A polymorphism influences MPO transcription and has been implicated in cancer risk. However, results from published studies on the association between the MPO -463G>A polymorphism and risk of cancer are conflicting. To derive a more precise estimation of association between the MPO -463G>A polymorphism and risk of cancer, we performed a meta-analysis based on 43 case-control studies, including a total of 14 171 cancer cases and 17 319 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the -463A allele had a 0.93-fold lower cancer risk in a dominant model (OR = 0.93, 95% CI = 0.87-1.00). In the stratified analyses, we observed a similar association in European populations (heterozygote comparison: OR = 0.90, 95% CI = 0.82-0.99) and hospital-based studies (dominant model: OR = 0.88, 95% CI = 0.79-0.99). When stratified by cancer type, however, no significant association was found. The results suggested that the MPO -463A allele does not contribute to the development of cancer. Additional well-designed large studies are required to validate these findings in different populations.