Background: Multiple sclerosis (MS) can affect adjustment at both the individual and couple level. Purpose: This study examined differences and associations between MS patient and spouse adjustment, and whether one partner’s adjustment predicts the other partner’s adjustment over time. Methods: A total of 160 couples at Time 1 and 98 couples at Time 2 completed questionnaires. Results: Mixed-model ANOVAs found that patients reported poorer adjustment than their spouse on a range of adjustment indicators and that positive affect and relationship satisfaction declined over time for both patients and spouses. Intraclass correlations found that patient and spouse scores on all adjustment indicators were related at Time 1. Multilevel modelling showed that one’s partner’s relationship satisfaction at Time 1 positively predicted one’s own relationship satisfaction at Time 2. Conclusions: The findings indicate that a focus on the interpersonal nature of adjustment to MS may be beneficial for future research and practice.