Objective External ventricular drain (EVD) placement is a common neurosurgical procedure performed in both the intensive care unit (ICU) and operating room (OR). The optimal setting for EVD placement in regard to safety and accuracy of placement is poorly defined. Methods A retrospective chart review was performed on 150 consecutive patients who underwent EVD placement at a tertiary care center from January of 2013 to February of 2014. Clinical and radiographic data were obtained and used to compare safety and accuracy of placement between EVDs placed in the ICU versus OR. Results One hundred and thirty eight patients were evaluated. Complications (hemorrhage, infection, non-functional drain) occurred in 21.5% of ICU placements and 6.7% of OR placements (p = 0.028). Grade 1, 2, and 3 placements occurred in 67.7%, 25.8%, and 6.5% of ICU placements, respectively, versus 55.6%, 42.2%, and 2.2% of OR placements (p = 0.258). No patient who received pre-placement antibiotics suffered a ventriculostomy associated infection (VAI). Conclusion Patients who underwent ventriculostomy placement in the ICU differed in important ways (i.e. indication for placement and the administration of pre-procedure prophylactic antibiotics) from patients treated in the OR. However, the available data suggests that complications of hemorrhage, infection, and non-functional drains may be mitigated by ventriculostomy placement in the OR.