Catheter-related bloodstream infections (CRBSIs) and exit-site infections (ESIs) are common complications associated with the use of central venous catheters for hemodialysis. The aim of this study was to analyze the impact of routine locking solutions on the incidence of CRBSI and ESI, in preserving catheter function, and on the rate of all-cause mortality in patients undergoing hemodialysis. We selected publications (from inception until July 2018) with studies comparing locking solutions for hemodialysis catheters used in patients undergoing hemodialysis. A total of 21 eligible studies were included, with a total of 4832 patients and 318,769 days of catheter use. The incidence of CRBSI and ESI was significantly lower in the treated group (citrate-based regimen) than in the controls (heparin-based regimen). No significant difference in preserving catheter function and all-cause mortality was found between the two groups. Our findings demonstrated that routine locking solutions for hemodialysis catheters effectively reduce the incidence of CRBSIs and ESIs, but our findings failed to show a benefit for preserving catheter function and mortality rates. Therefore, further studies are urgently needed to conclusively evaluate the impact of routine locking solutions on preserving catheter function and improving the rates of all-cause mortality.