Background. ECG guidance is widely used for positioning central venous catheters (CVCs) in the superior vena cava. We noticed a higher incidence of a more perpendicular angle between the catheter tip and the vessel wall after left-sided ECG-guided catheter positioning. To investigate the value of left-sided ECG guidance, we performed this prospective study.Methods. Of 114 patients, 53 were randomized to right and 61 to left internal jugular vein catheterization using a triple lumen catheter. Three methods to ascertain catheter tip position were sequentially applied in each patient, and the insertion depths (ID) obtained using each of the three methods were recorded: (i) ECG guidance with a Seldinger guide wire (ID-A); (ii) ECG guidance with saline 10% used as an exploring electrode (ID-B); (iii) from position ID-B, the catheter was rotated and advanced until all three lumina could be aspirated easily. The catheter was fixed in that position (ID-C). To determine final catheter tip position, intraoperative transoesophageal echocardiography (TOE) and a postoperative chest X-ray (CXR) were performed.Results. The depth of insertion of a catheter using the three methods varied significantly in left-sided (P<0.001), but not in right-sided catheters. Forty-eight of 57 (84%) left-sided CVCs, correctly positioned according to ECG guidance, had to be advanced further to achieve free aspiration through all three lumina. By this stage, five of the catheter tips had been positioned in the upper right atrium as demonstrated by TOE. There were 13 malpositions (23%) after left-sided insertion. In nine catheter malpositions, undetected by ECG guidance, the angle between the catheter tip and the lateral wall of the superior vena cava exceeded 40degrees on CXR.Conclusions. Intra-atrial ECG does not detect the junction between the superior vena cava and right atrium. It is not a reliable method for confirming position of left-sided CVCs. Post-procedural CXRs are recommended for left-sided, but not right-sided CVCs.