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Yanni Shi,1 Kezhong Zhang,2 Ming Ye3 1School of Stomatology, Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Department of Neurosurgery, The First Affiliated Hospital of Suzhou University, Suzhou, 215000, People’s Republic of ChinaCorrespondence: Kezhong Zhang; Ming Ye Email zhangkezhong9@126.com; yeming@suda.edu.cnIntroduction: The relationship between the risk of Parkinson disease and well-water consumption has been extensively studied, but the results have been contradictory. Therefore, we conducted a meta-analysis of observational studies to systematically assess the relationship between well-water consumption and Parkinson disease risk.Methods: We followed the PRISMA checklist in completing the meta-analysis. We searched two electronic databases (PubMed, EBSCO, EMBASE and Cochrane) from establishment to October, 2021, to identify relevant studies linking well-water drinking to Parkinson risk. We used a random-effects model to calculate the overall odds ratio (OR) with 95% confidence interval (CI). To reduce intragroup heterogeneity, we conducted subgroup analyses according to the research design and geographic area.Results: After careful review, a total of 15 case–control-designed studies included data suitable for our meta-analysis. The total number of cases and total controls that contribute to the combined OR were 2182 and 2456. The combined OR for ever well-water drinkers versus non-drinkers was 1.16 (95% CI: 0.97– 1.39, I2 = 44.52%). In subgroup analysis by geographic area, a significant association was observed in studies conducted in Asia (OR 1.29, 95% CI: 1.05– 1.58, I2 = 0.0%, p for heterogeneity = 0.460) but not in studies conducted in America (OR 0.97, 95% CI: 0.76– 1.24, I2 = 41.2%, p for heterogeneity = 0.164). In subgroup analysis by study design, a borderline significant association emerged in hospital-based case–control studies (OR 1.31, 95% CI: 1.04– 1.65, I2 = 40.9%, p for heterogeneity = 0.118) but not in population-based case–control studies (OR 0.96, 95% CI: 0.73– 1.26, I2 = 41.1%, p for heterogeneity = 0.165).Discussion: Our results indicate that there is no significant correlation between well-water consumption and PD risk.Keywords: Parkinson’s disease, well-water consumption, meta-analysis, risk factor