Abstract Introduction Which particular arterial catheter site is associated with a higher risk of infection remains controversial. The Centers for Disease Control and Prevention guidelines of 1996 and the latest guidelines of 2002 make no recommendation about which site or sites minimize the risk of catheter-related infection. The objective of the present study was to analyze the incidence of catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) of arterial catheters according to different access sites. Methods We performed a prospective observational study of all consecutive patients admitted to the 24 bed medical and surgical intensive care unit of a 650 bed university hospital during three years (1 May 2000 to 30 April 2003). Results A total of 2,018 patients was admitted to the intensive care unit during the study period. The number of arterial catheters, the number of days of arterial catheterization, the number of CRLIs and the number of CRBSIs were as follows: total, 2,949, 17,057, 20 and 10; radial, 2,088, 12,007, 9 and 3; brachial, 112, 649, 0 and 0; dorsalis pedis, 131, 754, 0 and 0; and femoral, 618, 3,647, 11 and 7. The CRLI incidence was significantly higher for femoral access (3.02/1,000 catheter-days) than for radial access (0.75/1,000 catheter-days) (odds ratio, 1.5; 95% confidence interval, 1.10–2.13; P = 0.01). The CRBSI incidence was significantly higher for femoral access (1.92/1,000 catheter-days) than for radial access (0.25/1,000 catheter-days) (odds ratio, 1.9; 95% confidence interval, 1.15–3.41; P = 0.009). Conclusion Our results suggest that a femoral site increases the risk of arterial catheter-related infection.