Abstract Objectives The objective of this meta-analysis of randomized trials was to evaluate if the administration of furosemide with matched hydration using the RenalGuard System reduces contrast-induced acute kidney injury (CI-AKI) in patients undergoing interventional procedures. Background CI-AKI is a serious complication following angiographic procedures and a powerful predictor of unfavorable early and long-term outcomes. Methods Online databases were searched up to October 1, 2016, for randomized controlled trials. The primary outcome was the incidence of CI-AKI, and the secondary outcomes were need for renal replacement therapy, mortality, stroke, and adverse events. Results A total of four trials (n = 698) published between 2011 and 2016 were included in the analysis and included patients undergoing percutaneous coronary procedures and transcatheter aortic valve replacement. RenalGuard therapy was associated with a lower incidence of CI-AKI compared with control treatment (27 of 348 7.76% patients vs. 75 of 350 21.43% patients; odds ratio OR: 0.31; 95% confidence interval CI: 0.19 to 0.50; I2  = 4%; p < 0.00001) and with a lower need for renal replacement therapy (2 of 346 0.58% patients vs. 12 of 348 3.45% patients; OR: 0.19; 95% CI: 0.05 to 0.76; I2  = 0%; p = 0.02). No major adverse events occurred in patients undergoing RenalGuard therapy. Conclusions The main finding of this meta-analysis is that furosemide with matched hydration by the RenalGuard System may reduce the incidence of CI-AKI in high-risk patients undergoing percutaneous coronary intervention or transcatheter aortic valve replacement. However, further independent high-quality randomized trials should elucidate the effectiveness and safety of this prophylactic intervention in interventional cardiology.