OBJECTIVE: The goal of this study was to explore the feasibility and accuracy of using a wearable mixed-reality holographic computer to guide external ventricular drain (EVD) insertion and thus improve on the accuracy of the classic freehand insertion method for EVD insertion. The authors also sought to provide a clinically applicable workflow demonstration. METHODS: Pre- and postoperative CT scanning were performed routinely by the authors for every patient who needed EVD insertion. Hologram-guided EVD placement was prospectively applied in 15 patients between August and November 2017. During surgical planning, model reconstruction and trajectory calculation for each patient were completed using preoperative CT. By wearing a Microsoft HoloLens, the neurosurgeon was able to visualize the preoperative CT-generated holograms of the surgical plan and perform EVD placement by keeping the catheter aligned with the holographic trajectory. Fifteen patients who had undergone classic freehand EVD insertion were retrospectively included as controls. The feasibility and accuracy of the hologram-guided technique were evaluated by comparing the time required, number of passes, and target deviation for hologram-guided EVD placement with those for classic freehand EVD insertion. RESULTS: Surgical planning and hologram visualization were performed in all 15 cases in which EVD insertion involved holographic guidance. No adverse events related to the hologram-guided procedures were observed. The mean ± SD additional time before the surgical part of the procedure began was 40.20 ± 10.74 minutes. The average number of passes was 1.07 ± 0.258 in the holographic guidance group, compared with 2.33 ± 0.98 in the control group (p < 0.01). The mean target deviation was 4.34 ± 1.63 mm in the holographic guidance group and 11.26 ± 4.83 mm in the control group (p < 0.01). CONCLUSIONS: This study demonstrates the use of a head-mounted mixed-reality holographic computer to successfully perform hologram-assisted bedside EVD insertion. A full set of clinically applicable workflow images is presented to show how medical imaging data can be used by the neurosurgeon to visualize patient-specific holograms that can intuitively guide hands-on operation. The authors also provide preliminary confirmation of the feasibility and accuracy of this hologram-guided EVD insertion technique.