The purpose of this study was to assess the long-term effectiveness of the antibiotic lock technique (ALT) in conjunction with systemic antibiotics for the salvage of long-term central venous catheter (CVC)-associated coagulase-negative Staphylococcus (CONS) bloodstream infections (BSIs) in children. A retrospective study of children with CVC-associated CONS BSIs treated with systemic vancomycin and ALT with vancomycin was carried out. The primary outcome was the immediate and 3-month success rate of salvage of the CVC. During the study period, 23 patients had persistent CONS bacteremia and were treated with ALT and systemic vancomycin. Of the 23 vancomycin lock treatments, eight catheters were removed during the acute event because of persistent bacteremia, six had relapse of CONS bacteremia within 30 days, and two had relapse within 90 days. Only seven CVCs (30%) were salvaged. Long-term transcutaneous CVCs (Hickman CVCs) were significantly associated with higher salvage rates than implantable ports (75% vs. 18%, P = 0.05). ALT with vancomycin for CVC-associated bacteremia has a limited long-term effectiveness, especially with implantable ports. Larger prospective studies are needed for the long-term evaluation of this technique.