BACKGROUND Scheduled replacement of central venous catheters and, by extension, arterial catheters, is not recommended because the daily risk of catheter-related infection is considered constant over time after the first catheter days. Arterial catheters are considered at lower risk for catheter-related infection than central venous catheters in the absence of conclusive evidence. OBJECTIVE To compare the daily risk and risk factors for colonization and catheter-related infection between arterial catheters and central venous catheters. METHODS We used data from a trial of seven intensive care units evaluating different dressing change intervals and a chlorhexidine-impregnated sponge. We determined the daily hazard rate and identified risk factors for colonization using a marginal Cox model for clustered data. RESULTS We included 3532 catheters and 27,541 catheter-days. Colonization rates did not differ between arterial catheters and central venous catheters (7.9% [11.4/1000 catheter-days] and 9.6% [11.1/1000 catheter-days], respectively). Arterial catheter and central venous catheter catheter-related infection rates were 0.68% (1.0/1000 catheter-days) and 0.94% (1.09/1000 catheter-days), respectively. The daily hazard rate for colonization increased steadily over time for arterial catheters (p = .008) but remained stable for central venous catheters. Independent risk factors for arterial catheter colonization were respiratory failure and femoral insertion. Independent risk factors for central venous catheter colonization were trauma or absence of septic shock at intensive care unit admission, femoral or jugular insertion, and absence of antibiotic treatment at central venous catheter insertion. CONCLUSIONS The risks of colonization and catheter-related infection did not differ between arterial catheters and central venous catheters, indicating that arterial catheter use should receive the same precautions as central venous catheter use. The daily risk was constant over time for central venous catheter after the fifth catheter day but increased significantly over time after the seventh day for arterial catheters. Randomized studies are needed to investigate the impact of scheduled arterial catheter replacement.