This paper describes a new noninvasive brain-actuated wheelchair that relies on a P300 neurophysiological protocol and automated navigation. When in operation, the user faces a screen displaying a real-time virtual reconstruction of the scenario and concentrates on the location of the space to reach. A visual stimulation process elicits the neurological phenomenon, and the electroencephalogram (EEG) signal processing detects the target location. This location is transferred to the autonomous navigation system that drives the wheelchair to the desired location while avoiding collisions with obstacles in the environment detected by the laser scanner. This concept gives the user the flexibility to use the device in unknown and evolving scenarios. The prototype was validated with five healthy participants in three consecutive steps: screening (an analysis of three different groups of visual interface designs), virtual-environment driving, and driving sessions with the wheelchair. On the basis of the results, this paper reports the following evaluation studies: 1) a technical evaluation of the device and all functionalities; 2) a users’ behavior study; and 3) a variability study. The overall result was that all the participants were able to successfully operate the device with relative ease, thus showing a great adaptation as well as a high robustness and low variability of the system.