There is little evidence on the role of prior infection in patients with external ventricular drains (EVDs) and lumbar drains (LDs). In this study, our aim is to investigate whether previous bacteremia is a risk factor for cerebrospinal fluid drain infection (CSFDI) in patients with EVDs and LDs and to describe the microorganisms implicated. We designed a retrospective, single-center cohort study. We recorded patients’ demographic and clinical characteristics, as well as microbiology laboratory data. We used non-parametric statistical methods to identify possible risk factors for CSFDI. We found 799 neurosurgical admissions during the study period, 70 of which fulfilled the inclusion criteria. Acinetobacter baumannii was the most frequent single pathogen isolated in the cerebrospinal fluid (CSF). Acinetobacter baumannii bacteremia was more common in patients with Acinetobacter baumannii CSFDI (p = 0.01). The distribution of the pathogens in the CSF differed from that of the pathogens isolated in blood (p = 0.001). In the univariate analysis, prior bacteremia was more common in patients with CSFDI (p = 0.027), but, in the multivariate model, prior bacteremia was not identified as an independent risk factor (OR = 0.456, CI: 0.138–1.512, p = 0.2). In an ICU population, the most frequently isolated pathogens were Gram-negative Enterobacteriaceae and Acinetobacter baumannii. Previous bacteremia was significantly more probable among patients with EVDs or LDs who developed a CSFDI, and its role warrants further investigation.