Differentiating true coagulase-negative staphylococcal infection from contamination has an important impact on therapeutic implications. Time to positivity reflects bacterial density and may help in the interpretation of blood cultures. We retrospectively reviewed the records of 272 patients from June 2005 to January 2008 for clinical characteristics, microbiological data, and therapeutic outcome. Four groups were identified. The first three groups, as follows, included patients with one positive quantitative blood culture: the low-colony-count group (<10 CFU/ml), the moderate-colony-count group (30 to 100 CFU/ml), and the high-colony-count group (>100 CFU/ml). The control group included patients with two positive quantitative blood cultures and definite coagulase-negative staphylococcal bloodstream infection. The high-colony-count group had shorter time to positivity (<16 h) than did the low-colony-count group (P < 0.0001). The low-colony-count group had a significantly longer time to positivity, >20 h (P ؍ 0.001), than did the moderate-colony-count group. Even though antibiotics were not provided in 71% of cases and central venous catheter was retained in 83%, the low-colony-count group had a favorable outcome, suggesting that <10 CFU/ml represents contamination. The high-colony-count group, similar to the positive control group, required antibiotics in 81% of cases and central venous catheter removal in 51% (P ؍ 0.001). A time to positivity of <16 h reflects high-grade bacteremia with CFU of >100. Similar to the positive control group, these patients required an active therapeutic approach. A time to positivity of >20 h indicates possible contamination with a CFU of <10, and active therapy may not be required.