Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality in haemodialysis patients with central venous catheters (CVCs). Antibiotic lock solutions (ALS), such as gentamicin and vancomycin, are widely used, yet comparative efficacy and resistance profiles remain unclear. This systematic review evaluated the effectiveness of gentamicin lock solutions versus vancomycin or other alternatives in preventing CRBSIs. A literature search across four databases (2009–2024) identified five eligible studies involving adult haemodialysis patients with CVCs. Included studies reported CRBSI rates associated with ALS use. Gentamicin demonstrated equal or superior efficacy to vancomycin, heparin, or other comparators, with added gram-negative coverage and lower cost. However, concerns about ototoxicity and resistance remain. Vancomycin was effective against gram-positive organisms but linked to higher vancomycin-resistant enterococci (VRE) risk in some settings. Both agents are effective, but gentamicin may offer a cost-effective alternative in appropriate settings. Further trials are needed to guide standardised ALS use. Keywords: CRBSI, antibiotic lock, gentamicin, vancomycin, haemodialysis, CVC.