There are limited data on the clinical significance of positive central venous catheter (CVC) tip cultures associated with concomitant negative blood cultures performed at the time of CVC removal. A retrospective cohort study of all patients who yielded isolated positive CVC tip cultures was conducted in a tertiary-care hospital with 2200 beds during a 10-year period. All patients with isolated positive CVC tip cultures were observed for the development of subsequent bacteraemia or fungaemia between 2 and 28 days after CVC removal. An isolated positive CVC tip culture was defined as a case in which (i) a CVC tip culture yielded > or = 15 colonies using a semiquantitative culture method and (ii) at least two sets of blood samples revealed no organism at, or close to, the time of CVC removal (48 h before to 48 h after CVC removal). During the study period, 312 patients with isolated positive CVC cultures were enrolled. Eight (2.6%; 95% CI 1.2-5.1) of the 312 patients yielding isolated bacterial or fungal CVC tip cultures developed subsequent bloodstream infection (BSI) caused by the same species as that isolated from the tip culture (Staphylococcus aureus, 1: Enterococcus spp.; 2: Pseudomonas aeruginosa; and 3: Candida spp.). Among 125 patients from whose CVC tips the above four organisms were grown, seven (12.3%) of 57 patients who did not receive appropriate antibiotic therapy within 48 h after CVC removal subsequently developed BSI, but only one (1.5%) of 68 patients who did receive appropriate therapy developed BSI (OR 0.11, p 0.02).