Objective: This study investigated the role of individual differences in neuroticism in conferring increased reactivity to the interpersonal antecedents for suicide proposed by the interpersonal theory of suicide. Method: Undergraduate students (N = 113) were screened and selected to form high (n = 58) and low (n = 55) neuroticism groups, and an experimental computer task was used to manipulate participants’ experience of thwarted belongingness and perceived burdensomeness. Participants’ self-reported desire to persist in the face of this induced interpersonal adversity was measured. Results: Results indicate that high neuroticism confers increased reactivity to the experimental induction of the interpersonal antecedents of suicidal ideation: Thwarted belongingness and perceived burdensomeness. Furthermore, this vulnerability corresponds to a diminished desire to persist with the task in the face of interpersonal adversity. Conclusions: Neuroticism confers vulnerability for suicidal desire via an increased reactivity to the proximal, causal risk factors proposed by the interpersonal theory of suicide. This has implications for considering how personality risk factors such as neuroticism may interact with proximal interpersonal risk factors to increase suicidal ideation.