Suicide research can be enhanced by an ability to safely manipulate putative causal variables. The present studies developed an experimental task to modify risk factors identified by the interpersonal theory of suicide (perceived burdensomeness and thwarted belongingness) and examine their hypothesized suppressive effect on persistence in adversity in undergraduate university students. Variables that may moderate the impact of these risk factors on persistence (zest for life and mindful awareness) were incorporated as potential resilience factors. Study 1 (N = 92) found elevated burdensomeness and diminished belongingness significantly impaired persistence. Additionally, these predicted effects were moderated by individual differences in zest for life. In Study 2 (N = 52), individuals trained in mindfulness prior to the experimental task displayed greater persistence relative to controls. Findings provide experimental support for the role of perceived burdensomeness and thwarted belongingness in the manner predicted by the interpersonal theory, and demonstrate a way to experimentally test the effects of resilience factors that reduce the impact of these interpersonal factors.