The goal of this research was to examine the possible benefits of adapting the Multi-Attribute Task Battery (MATB-II) in a virtual reality (VR) environment to provide an immersive and ecological platform for studies on mental workload in the aerospace domain. The original desktop MATB-II has many advantages, but the level of immersion remains moderate, and the computer screen greatly reduces the spatial dimension existing in real environments such as the cockpit. Thirty-one participants performed an experiment during which we compared the original MATB-II with the new virtual version, called “MATB-II VR”. We used subjective, performance, and cardiovascular measurements. The virtual MATB-II was performed without (“MATB-II VR No Touch”) and with tactile feedback (“MATB-II VR Touch”). In general, the results showed that mental and physical efforts were higher and performances lower with the virtual version. Heart rate was higher with the virtual version, supporting the idea that such environment is more challenging. The individual performance in the desktop and the virtual environments correlated well, showing that our virtual version engaged analog physical and cognitive abilities as compared with the original version. Interestingly, performance during MATB-II VR was well predicted by basic mental rotation performance assessed with a neuropsychological task.