Cerebrospinal fluid (CSF) culture is the gold standard for diagnosing postoperative central nervous system infection. The time to positivity (TTP) of an automated continuous blood culture system may indicate the original concentration of the organism. Coagulase-negative Staphylococcus (CoNS), the common organism recovered in CSF, poses difficulty in differentiating infection from contamination. This study investigated the TTP of CSF culture with CoNS and its relationship to clinical parameters and prognosis. Adult neurosurgical patients with CoNS who recovered via the use of CSF culture in BacT/ALERT Pediatric FAN blood culture bottles and were admitted from September 2013 to July 2015 were enrolled. The demographics, clinical and microbiological data, and treatment were reviewed, and the TTP of each culture was retrieved. Thirty-nine adult patients with CoNS recovered from CSF culture were included. The TTP ranged from 7.68 to 57.36 hours. A univariate logistic regression analysis indicated patients with rapid TTP (<21.5 hours) compared with those with longer TTP were more likely to be female, show an effective response to antibiotic therapy within 7 days, have clean-contaminated surgical incisions, and show CSF leak. A multivariate logistic regression analysis indicated that being female, an effective antibiotic therapy within 7 days, and clean-contaminated surgical incisions were independent predictors of rapid TTP. Targeted antibiotic therapy was more likely to be beneficial to patients with a rapid TTP within 7days, which suggested that CoNS with a rapid TTP represents the pathogen of central nervous system infection rather than contamination in neurosurgical patients.