Increasing the level of automation in air traffic management is seen as a measure to increase the performance of the service to satisfy the predicted future demand. This is expected to result in new roles for the human operator: he will mainly monitor highly automated systems and seldom intervene. Therefore, air traffic controllers (ATCos) would often work in a supervisory or control mode rather than in a direct operating mode. However, it has been demonstrated how human operators in such a role are affected by human performance issues, known as Out-Of-The-Loop (OOTL) phenomenon, consisting in lack of attention, loss of situational awareness and de-skilling. A countermeasure to this phenomenon has been identified in the adaptive automation (AA), i.e., a system able to allocate the operative tasks to the machine or to the operator depending on their needs. In this context, psychophysiological measures have been highlighted as powerful tool to provide a reliable, unobtrusive and real-time assessment of the ATCo’s mental state to be used as control logic for AA-based systems. In this paper, it is presented the so-called “Vigilance and Attention Controller”, a system based on electroencephalography (EEG) and eye-tracking (ET) techniques, aimed to assess in real time the vigilance level of an ATCo dealing with a highly automated human–machine interface and to use this measure to adapt the level of automation of the interface itself. The system has been tested on 14 professional ATCos performing two highly realistic scenarios, one with the system disabled and one with the system enabled. The results confirmed that (i) long high automated tasks induce vigilance decreasing and OOTL-related phenomena; (ii) EEG measures are sensitive to these kinds of mental impairments; and (iii) AA was able to counteract this negative effect by keeping the ATCo more involved within the operative task. The results were confirmed by EEG and ET measures as well as by performance and subjective ones, providing a clear example of potential applications and related benefits of AA.