Objective: To evaluate the feasibility and usability of an assistive technology (AT) prototype designed to be operated with conventional/alternative input channels and a P300-based brain-computer interface (BCI) in order to provide users who have different degrees of muscular impairment resulting from amyotrophic lateral sclerosis (ALS) with communication and environmental control applications. Design: Proof-of-principle study with a convenience sample. Setting: An apartment-like space designed to be fully accessible by people with motor disabilities for occupational therapy, placed in a neurologic rehabilitation hospital. Participants: End-users with ALS (N=8; 5 men, 3 women; mean age +/- SD, 60 +/- 12y) recruited by a clinical team from an ALS center. Interventions: Three experimental conditions based on (1) a widely validated P300-based BCI alone; (2) the AT prototype operated by a conventional/alternative input device tailored to the specific end-user's residual motor abilities; and (3) the AT prototype accessed by a P300-based BCI. These 3 conditions were presented to all participants in 3 different sessions. Main Outcome Measures: System usability was evaluated in terms of effectiveness (accuracy), efficiency (written symbol rate, time for correct selection, workload), and end-user satisfaction (overall satisfaction) domains. A comparison of the data collected in the 3 conditions was performed. Results: Effectiveness and end-user satisfaction did not significantly differ among the 3 experimental conditions. Condition III was less efficient than condition II as expressed by the longer time for correct selection. Conclusions: A BCI can be used as an input channel to access an AT by persons with ALS, with no significant reduction of usability.