Incidence of primary mechanical complications and malpositions associated with landmark-guided central venous access procedures (CVAP) performed by experienced operators. Prospective 5-year observational study on two intensive care units. Only CVAPs using Seldinger technique were evaluated. Age, gender, puncture site, number of cannulation attempts, and complications within 24 hours and malpositions were recorded. 782 CVAPs in females aged 9-92 yrs and 1012 CVAPs in males aged 6-89 yrs. We analyzed 1794 (1017 right- and 777 left-sided CVAP), of which 87.7% were accomplished without adverse events. More than one cannulation attempt was a risk factor for failed catheterization, other mechanical complications but not for malposition. Complications/malpositions were encountered in 220 CVAPs.In 51 CVAPs (2.8%) the cannulation failed at the attempted site, here 18 CVAPs were accompanied by further complications (35.3%). Otherwise, the rate for mechanical complications was low (3.3%). The most common mechanical complications (n = 127) were arterial punctures (n = 52; 2.9%), including four arterial cannulations (0.2%), and pneumothorax (n = 9; 0.6%). There was significant risk for arterial puncture with the internal jugular vein approach in comparison to the innominate vein (p = 0.004), but not to the subclavian vein (p = 0.065). Male patients had a lower risk for failure (2.1%) than females (3.8%, p = 0.028). One-hundred-twenty-one central venous catheters were malpositioned (6.7%) of which 35 were related to the left internal jugular vein. Even experienced operators cause a considerable number of early mechanical complications and malpositions. After two unsuccessful cannulation attempts failure and associated complications are very likely.