Catheter-related bloodstream infection (CRBSI) with hemodialysis catheters are associated with increased mortality, morbidity and pose significant financial burden on healthcare. Antibiotic and antimicrobial locking solutions are effective in reducing risk of CRBSI. From inception to April 2020, we looked for relevant clinical controlled trials throughout the following databases: EBSCO, PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, clinicaltrial.gov, and Google Scholar performing a metanalysis comparing antibiotic and antimicrobial lock solutions to heparin. Twenty-six studies with 4,967 patients reported the incidence of catheter-related bacteremia (CRB). The overall pooled risk ratio (RR) showed that the intervention group was associated with a significantly lower incidence of CRB by 30% compared with heparin (RR = 0.30, 95% confidence interval [CI] [0.25, 0.36], p < 0.001). Subgroup analysis showed that administration of antibiotic regimens led to a decreased risk of CRB episodes by 28% compared with the heparin group (RR = 0.28, 95% CI [0.21, 0.37], p < 0.0001). Antimicrobial solutions was associated with reduced risk of CRB by 32% compared with patients of the control group (RR = 0.32, 95% CI [0.25, 0.41], p < 0.0001). A test of subgroup differences was revealed no significant favoring of any of the two interventions. Both antibiotic and antimicrobial solutions are effective in reducing CRBSI.