An infrared based frameless stereotactic navigation device (Easy Guide Neuro) was investigated for its clinical applicability, registration/application accuracy and limitations in a standard operating room set-up. In a five-month period 40 frameless stereotactic procedures (23 female, 17 male, mean age 46.4, yrs range 10-83) including 36 craniotomies and 4 spinal surgery procedures were performed. Image registration, data transfer and operation planning using skin fixed fiducials (between 5-10, mean 6.6) and CCT in 12 patients/MRI in 28 patients, generally was done the day before surgery. Clinical applicability was proven in all procedures with an additional time for pre-operative imaging and system application in the OR of 50 min mean (35-120 range). A useful registration was achieved in 39/40 patients (97.5%) with a registration accuracy of 3.4 mm (range 1.8-6.7) for brain surgery cases and 14.4 mm (6.8-25) for spine cases. This resulted in intra-operative application accuracy values for brain surgery of 4.2 mm mean (range 1-12). Enhanced registration/application accuracy values over the test period from 4.2/3.8 mm mean (Cases 1-20) up to 3.2/2 mm mean (Cases 21-40) was observed. In spinal surgery an application accuracy of 11.3 mm mean (range 5-20) was found. An intra-operative re-calibration because of system-head drift was necessary in none of the patients, nevertheless, application accuracy degradation due to brain shift was detected in every case. In conclusion, the system allowed a time sufficient accurate frameless intra-operative localisation guidance in cavernoma, meningioma, glioma, and brain metastasis surgery. In spinal surgery, the application accuracy exceeded clinical usefulness due to high registration inaccuracy using skin markers.