A growing body of literature suggests that virtual reality is a successful tool for exposure therapy in the treatment of anxiety disorders. Virtual reality (VR) researchers posit the construct of presence, defined as the interpretation of an artificial stimulus as if it were real, to be a presumed factor that enables anxiety to be felt during virtual reality exposure therapy (VRE). However, a handful of empirical studies on the relation between presence and anxiety in VRE have yielded mixed findings. The current study tested the following hypotheses about the relation between presence and anxiety in VRE with a clinical sample of fearful flyers: (1) presence is related to in-session anxiety; (2) presence mediates the extent that pre-existing (pre-treatment) anxiety is experienced during exposure with VR; (3) presence is positively related to the amount of phobic elements included within the virtual environment; (4) presence is related to treatment outcome. Results supported presence as a factor that contributes to the experience of anxiety in the virtual environment as well as a relation between presence and the phobic elements, but did not support a relation between presence and treatment outcome. The study suggests that presence may be a necessary but insufficient requirement for successful VRE.