In recent years, clinical studies have begun to demonstrate the effectiveness of VR as an intervention tool for a variety of neurological conditions. There remain, however, a number of important issues that must be addressed in order to determine how widely VR-based intervention should be applied, and the user and platform characteristics that may be important when using VR in clinical settings. One of the unresolved issues that must be addressed is the suitability of particular VR platforms in relation to the therapeutic goals one wishes to achieve. Studying and identifying the characteristics of each platform may assist the therapist in choosing a suitable VR platform for the patient's needs. The purpose of this paper is to describe the results of a study of healthy participants (N = 89) using 2 different VR platforms in combination with 1 of the 2 virtual environments that was designed to compare the sense of presence, incidence of side effects, perceived exertion, and performance. The data demonstrate significant differences in some of the key characteristics of both VR platforms and environments as they affect participants' sense of presence, performance, side effects, and exertion. We conclude that when seeking a suitable VR therapeutic application, the user's characteristics together with attributes of the VR platform must be taken into consideration since both appear to have an impact on key outcome measures.