Background: Recent studies have suggested a potential increased risk of acute kidney injury ( AKI) among proton-pump inhibitor (PPI) users. However, the present results are conflicting. Thus, we performed a meta-analysis to investigate the association between PPI therapy and the risk of AKI. Methods: EMBASE, PubMed, Web of Science, and Cochrane Library databases (up to September 23, 2016) were systematically searched for any studies assessing the relationship between PPI use and risk of AKI. Studies that reported relevant risk ratios (RRs), odds ratios, or hazard ratios were included. We calculated the pooled RRs with 95% confidence intervals (CI) using a random-effects model of the meta-analysis. Subgroup analysis was conducted to explore the source of heterogeneity. Results: Seven observational studies (five cohort studies and two case-control studies) were identified and included, and a total of 513,696 cases of PPI use among 2,404,236 participants were included in the meta-analysis. The pooled adjusted RR of AKI in patients with PPIs use was 1.61 (95% CI: 1.16-2.22; I-2= 98.1%). Furthermore, higher risks of AKI were found in the subgroups of cohort studies, participant's average age,60 years, participants with and without baseline PPI excluded, sample size,300,000, and number of adjustments >= 11. Subgroup analyses revealed that participants with or without baseline PPI excluded might be a source of heterogeneity. Conclusion: PPI use could be a risk factor for AKI and should be administered carefully. Nevertheless, some confounding factors might impact the outcomes. More well-designed prospective studies are needed to clarify the association.