Background and purpose Accurate placement of an external ventricular drain (EVD) for the treatment of hydrocephalus is of paramount importance for its functionality and in order to minimize morbidity and complications. The aim of this study was to compare two different drain insertion assistance tools with the traditional free-hand anatomical landmark method, and to measure efficacy, safety and precision. Methods Ten cadaver heads were prepared by opening large bone windows centered on Kocher's points on both sides. Nineteen physicians, divided in two groups (trainees and board certified neurosurgeons) performed EVD insertions. The target for the ventricular drain tip was the ipsilateral foramen of Monro. Each participant inserted the external ventricular catheter in three different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous trajectories; time to proceed; radiation exposure of patients and physicians; distance of the catheter tip to target and size of deviations projected in the orthogonal plans were measured and compared. Results Insertion using XCT increased the probability of ventricular puncture from 69.2 to 90.2 % (p=0.02). Non-assisted placements were significantly less precise (catheter tip to target distance 14.3±7.4 mm versus 9.6±7.2 mm, p=0.0003). The insertion time to proceed increased from 3.04±2.06 min. to 7.3±3.6 min. (p<0.001). The X-ray exposure for XCT was 32.23 mSv, but could be reduced to 13.9 mSv if patients were initially imaged in the hybridoperating suite. No supplementary radiation exposure is needed for NN if patients are imaged according to a navigation protocol initially. Conclusion This ex vivo study demonstrates a significantly improved accuracy and safety using either NN or XCTassisted methods. Therefore, efforts should be undertaken to implement these new technologies into daily clinical practice. However, the accuracy versus urgency of an EVD placement has to be balanced, as the image-guided insertion technique will implicate a longer preparation time due to a specific image acquisition and trajectory planning.