Despite an established link between personality traits and relationship outcomes, few studies have examined whether personality impacts outcomes of couple interventions. Given the growing popularity of online relationship services, we examined whether Five-Factor Model personality traits moderated change in relationship satisfaction, relationship confidence, and depressive symptoms of couples completing the web-based OurRelationship program. Three-hundred couples were randomly assigned to the program or to a waitlist control group and were repeatedly assessed using self-report measures of relationship satisfaction, relationship confidence, and depressive symptoms. Overall, results suggested that Five-Factor Model personality traits are mostly unrelated to changes in individual and interpersonal well-being. However, across conditions, higher levels of neuroticism predicted a smaller decrease in depressive symptoms (Aim 1). In addition, the effects of the intervention (versus control) on change in relationship satisfaction and depressive symptoms were moderated by neuroticism, such that high levels of neuroticism predicted stronger intervention effects on relationship satisfaction and depressive symptoms (Aim 2). Lastly, the effects of conscientiousness and neuroticism on changes in depressive symptoms were partially mediated by baseline levels of depressive symptoms. These findings suggest that the OurRelationship program may already contain elements that address behaviors associated with high or low personality trait levels and that higher levels of neuroticism may actually augment intervention effects on relationship satisfaction and depressive symptoms. Given the inconsistency of our findings across the various outcomes as well as personality, further research is needed to determine the role of personality in web-based couple interventions.