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OBJECTIVEExternal ventricular drain (EVD) placement is a common neurosurgical procedure. While this procedure is simple and effective, infection is a major limiting factor. Factors predictive of infection reported in the literature are not conclusive. The aim of this retrospective, single-center large series was to assess the rate and independent predictors of ventriculostomy-associated infection (VAI).METHODSThe authors performed a retrospective chart review of consecutive patients who underwent EVD placement between January 2012 and January 2018.RESULTSA total of 389 patients were included in the study. The infection rate was 3.1% (n = 12). Variables that were significantly associated with VAI were EVD replacement (OR 10, p = 0.001), bilateral EVDs (OR 9.2, p = 0.009), duration of EVD placement (OR 1.1, p = 0.011), increased CSF output/day (OR 1.0, p = 0.001), CSF leak (OR 12.9, p = 0.001), and increased length of hospital stay (OR 1.1, p = 0.002). Using multivariate logistic regression, independent predictors of VAI were female sex (OR 7.1, 95% CI 1.1–47.4; p = 0.043), EVD replacement (OR 8.5, 95% CI 1.44–50.72; p = 0.027), increased CSF output/day (OR 1.01, 95% CI 1.0–1.02; p = 0.023), and CSF leak (OR 15.1, 95% CI 2.6–87.1; p = 0.003).CONCLUSIONSThe rate of VAI was 3.1%. Routine CSF collection (every other day or every 3 days) and CSF collection when needed were not associated with VAI. The authors recommend CSF collection when clinically needed rather than routinely.