Purpose/Objective: While personality traits have been well-documented to be related to resilience in several populations, they have yet to be explored in people with multiple sclerosis (PwMS). As such, this study aimed to understand how personality traits are associated with MS-related resilience after considering the independent contributions of self-efficacy, a significant component of the biopsychosocial model of resilience in MS, and demographic and disease characteristics. Research Method/Design: Participants (N = 112) were PwMS who completed a 1-time cross-sectional study. Resilience was measured using the MS Resiliency Scale, while personality traits and self-efficacy were assessed using the NEO-Five Factor Inventory-3 and University of Washington Self-Efficacy Scale, respectively. An ordinary least squares linear regression was run to examine the relationship between resilience, personality traits, self-efficacy, and demographic and disease characteristics. Results: Self-efficacy (b = .40, 95% CI [.17, .63], p < .001) and neuroticism (b = −.35, 95% CI [−.51, −.19], p < .001), as well as being married (b = .06, 95% CI [.12, 8.00], p = .044) were significantly related to resilience. While extraversion, conscientiousness, and agreeableness were associated with resilience on a bivariate level, they were not significant in the multivariate model. Conclusions/Implications: This study highlights how neuroticism, along with self-efficacy and marital status, plays a role in MS-related resilience. While further research is needed, these findings may help inform future resilience-building interventions or identify individuals at greater risk for lower levels of resilience.