BACKGROUND AND PURPOSE: Ventriculostomy-associated infection (VAI) is a serious complication of external ventricular drainage (EVD). Infection rates and risk factors are variable in the literature due to heterogeneity of EVD procedures and management. This study aimed to investigate the incidence of VAI and its associated factors in two institutions with identical EVD procedural and management protocols.METHODS: The authors reviewed the medical records of patients older than 18 years who received EVD placements between January 2015 and December 2020 in two institutions under a single healthcare system. RESULTS: A total of 216 patients with 328 catheters was included for analysis. Twenty-three VAIs were identified, a 10.6% VAI rate. VAI was associated with a shorter duration of first EVD (9.7 days vs. 11.8 days, P = 0.018), a longer total EVD duration (28.0 days vs. 16.1 days, P < 0.001), a longer procedural time (72 minutes vs. 40 minutes, P < 0.001), catheterization at non-Kocher’s points (34.7% vs. 12.5%, P = 0.010), cerebrospinal fluid (CSF) leak (8.7% vs. 1.6%, P = 0.030), craniotomy (87.0% vs. 61.7%, P = 0.020), and other systemic infections (30.4% vs. 9.3%, P = 0.012). On multivariate analysis, the first EVD duration (OR = 0.095, P < 0.001), total EVD duration (OR 1.128, P < 0.001), EVD placement at non-Kocher’s point (OR 4.545, P = 0.012), and other systemic infections (OR = 5.117, P = 0.024) were associated independently with VAI. There was no statistical difference in VAI rate between patients with or without prophylactic EVD exchange at 14 days (6.8% vs. 12.6%, P = 0.247).CONCLUSIONS: Concomitant systemic infection and placement of an EVD catheter at a non-Kocher’s point were independently associated with VAI. Prophylactic EVD exchange at 14 days did not lower VAI rate.