This study evaluated the clinical validity of frameless stereotaxy using high-field intraoperative magnetic resonance (iMR) imaging combined with an in-room neuronavigation system. A 1.5 Tesla MR scanner in conjunction with a ceiling-mounted neuronavigation system was used during 32 frameless stereotaxy procedures consisting of 19 brain biopsies and 13 catheter placements between April 2002 and mid-October 2003. Evaluation of the procedure was based on either the rate of histological diagnostic yield or the ability to accurately position the catheter in the target region. This technique allowed successful registration with a mean error of 1.2 ± 0.8 mm and resulted in successful placement of the instrument within the target tissue. Intraoperatively, frozen section analysis showed all biopsy samples contained pathological tissue and locations of sampling points were confirmed by iMR imaging. Specific final diagnosis was made in all 19 brain biopsies. The tip of the catheter was successfully placed into the target in all 13 patients confirmed by iMR imaging. The catheter was repositioned based on iMR imaging in four of 13 patients, increasing the rate of successful placement. There were no procedure-related neurological deficits or mortality, but we encountered two cases of wound infection, one needing surgical revision. Total additional procedure time related to the induction of iMR imaging was 76.7 ± 23.3 minutes. This initial experience of the combination of conventional frameless stereotaxy and high-field iMR imaging improved the quality of frameless stereotaxy with low morbidity and mortality, but did not translate into a significant reduction of procedure-related time.