We conducted a meta-analysis to explore the association between the use of different anti-ulcer agents and the risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), and decline in glomerular filtration rate (GFR) in various study populations.PubMed, Embase, and the Cochrane Library were searched for relevant entries up to July 1, 2017. The primary outcomes of the meta-analysis were risk ratios (RRs) of CKD, ESRD, and decline in GFR. We also investigated the heterogeneity of the meta-analysis by subgroup analysis and meta-regression analysis.A total of 662,624 individuals were enrolled in five trials. Compared with non-PPI users, PPI users had a higher trend of CKD (RR = 1.16, 95% CI 1.07-1.25, P < 0.001), especially ESRD (RR = 1.81, 95% CI 1.59-2.06, P < 0.001). There was an elevated risk of adverse renal outcome among participants receiving PPI and not H2RA (CKD: RR = 1.28, 95% CI 1.24-1.33, P < 0.001; ESRD: RR = 1.39, 95% CI 1.17-1.64, P < 0.001; GFR: RR = 1.31, 95% CI 1.26-1.36, P < 0.001). However, H2RA users were not associated with CKD when compared with non-H2RA users (RR = 1.02, 95% CI 0.83-1.25, P = 0.855). In subgroup analysis, the average age of individuals and drug dosage had no influence on the risk of CKD, while duration of PPI exposure from 31 to 720 days is a potential factor in progression to ESRD (P < 0.001).Chronic PPI use, but not H2RAs, is associated with deterioration in kidney function.