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This Practice Point commentary discusses the findings and limitations of a meta-analysis that evaluated the use of prophylactic antibiotics for hemodialysis catheters. Use of prophylactic topical antibiotics at the catheter exit site was associated with a significant reduction in catheter-related bacteremia, exit-site infections, catheter removals due to secondary complications, hospitalizations for infection, and patient mortality. Use of prophylactic intraluminal antibiotic instillation was associated with a significantly reduced risk of catheter-related bacteremia and need for catheter removal. This commentary highlights the issues that should be considered when interpreting and generalizing these results, including the variability of antibiotic type and catheter type (nontunneled vs tunneled), the use of co-interventions in the various trials, and potential publication bias. The known benefits of prophylactic antibiotic use in patients with hemodialysis catheters are strongly supported by this meta-analysis.