Purpose: Pancreatic cancer (PC) is a devasting disease of which mortality almost parallels its incidence. Pancreatic cancer tissue may express aberrantly methylated NPTX2, but it is unclear what the consequences of this are. The purpose of the present study was to assess the diagnostic performance of methylated NPTX2 in PC diagnosis. Methods: We conducted a comprehensive search of PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and the Cochrane Library for published studies from inception to July 15, 2020. Using STATA 13.0, diagnostic OR (DOR) and AUC (Area Under the Curve of Receiver Operating Characteristic) were calculated to evaluate the diagnostic efficacy. Results: Nine studies were found eligible for the meta-analysis. The overall results of DOR and AUC were 11 (95%CI: 4-26) and 0.80, respectively. These data indicate that aberrantly methylated NPTX2 can correctly predict PC. Subgroup analysis revealed that quantitative real-time methylation-specific PCR (QMSP) had the highest diagnostic value for differentiating pancreatic cancer from chronic pancreatitis using a laboratory method. Furthermore, the detection of hypermethylated NPTX2 found in plasma was suggested to be a promising diagnostic biomarker, though a meta-analysis was not feasible due to the limited number of samples. The Deeks’ funnel map revealed no obvious public bias in the literature. Conclusion: aberrantly methylated NPTX2 has high sensitivity and specificity for the diagnosis of pancreatic cancer. However, further research is required to validate the use of methylated NPTX2 as a biomarker in the clinical diagnosis of pancreatic cancer.