AIM: Proton pump inhibitors (PPIs) were widely used around the world. Studies suggested conflicting results between PPIs treatment and the risk of dementia. This study examined the association between PPIs and dementia risk by mining the US FDA Adverse Event Reporting System (FAERS) database. METHODS: We identified six PPI agents and adverse reports of dementia based on FAERS database from 2004 to 2019. We employed reporting odds ratio (ROR) and proportional reporting ratio (PRR) to detect the signals of dementia relevant to PPIs. We also analyzed characteristics of PPI reports, compared dementia events between short- and long- duration PPIs treatment. RESULTS: We identified 2104 dementia cases with PPIs treatment. We did not detect significant signals between PPIs and dementia, ROR = 0.99, 95%CI 0.94 - 1.03, PRR = 0.99, 95%CI 0.95 - 1.03, even in gastroesophageal reflux disease cases ROR = 0.65, 95%CI 0.58 - 0.73, PRR = 0.67, 95%CI 0.60 - 0.74. No significant differences of dementia events were detected between short- and long- duration groups, the OR (95%CI) of the 6 months, 1 year, 3 years and 5 years comparison were 0.85 (0.68 - 1.06), 0.92 (0.71 - 1.18), 0.81 (0.57 - 1.15) and 0.79 (0.52 - 1.22), respectively. CONCLUSIONS: Based on the current FAERS data mining, we discovered no association between PPIs use and the risk of dementia.