Objectives: MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively (\"in-and-out\") in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators. Methods: Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators – attending (AR) and resident radiologists (RR) as well as medical students (MS) – performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm). Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0). Results: Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min: sec) differed significantly (p<0.01). Mean overall rating was 4.2. The average operator would use the system again (4.8) and stated that the outcome justifies the extra effort (4.4). Lowest agreement was reported for the robustness against external perturbations (2.8). Conclusions: The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore) MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between groups with different expertise there were significant differences in experimental procedure times but not in the number of successful biopsies.