This article focuses on evaluating the usability of an intelligent wheelchair (IW) in both real and simulated environments. The wheelchair is controlled at a high-level by a flexible multimodal interface, using voice commands, facial expressions, head movements and joystick as its main inputs. A quasi-experimental design was applied including a deterministic sample with a questionnaire that enabled to apply the System Usability Scale. The subjects were divided in two independent samples: 46 individuals performing the experiment with an IW in a simulated environment (28 using different commands in a sequential way and 18 with the liberty to choose the command); 12 individuals performing the experiment with a real IW. The main conclusion achieved by this study is that the usability of the IW in a real environment is higher than in the simulated environment. However, there were not statistical evidences to affirm that there are differences between the real and simulated wheelchairs in terms of safety and control. Also, most of users considered the multimodal way of driving the wheelchair very practical and satisfactory. Thus, it may be concluded that the multimodal interfaces enables very easy and safe control of the IW both in simulated and real environments.