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Our aim was to compare difficulties in vascular access interventions in infants with and without Down Syndrome (DS) undergoing congenital heart surgery.The anesthesia records of infants with DS undergoing congenital heart surgery (Group DS, n=61) were reviewed and matched with records of infants without DS (Group ND, n=61). Vascular cannulation sites, the experience of the anesthesiologists performing each procedure, the number of clinicians who attempted each procedure until it was successfully performed, and the number of attempts for each catheterization were recorded.The rate of unsuccessful peripheral venous cannulation in any of the four extremities was higher in Group DS (P=0.026). The success rate of radial artery cannulation was lower in Group DS (P=0.048). Although the total number of attempts for arterial cannulation was higher in Group DS, the difference was not statistically significant (P=0.058). However, in Group DS, the clinician who was able to cannulate the artery successfully required a significantly higher number of attempts at cannulation (P=0.011). For central venous catheterization, cannulation site and the number of attempts required before success was achieved were similar in both groups. The specialist-to-resident ratio was higher in Group DS (P=0.037).Our results indicate a trend toward clinicians having more difficulty performing arterial and peripheral venous catheterizations in infants with DS compared with performing the same procedure in infants without DS. Anesthesiologists should be prepared for catheterization difficulties in this patient population. In infants with DS, we recommend that catheterizations be performed by more experienced physicians.