Objective: Despite disease modifying therapies’ (DMT) demonstrated efficacy for treating relapsing MS, around 40% of patients discontinue use. This study aimed to understand the mechanism of action of Motivational Interviewing plus cognitive behavioral therapy (MI-CBT) in a previously conducted randomized controlled trial in which the MI-CBT intervention successfully promoted DMT re-initiation of participants compared to a treatment as usual (TAU) condition. Method: This secondary analysis (N=91) explored changes in motivation (a single item motivation “ruler” [Mot ∆], and the Brief Motivation Scale [BMS∆]), autonomous motivation (AR∆), personal control (PC∆), treatment control (TC∆), and confidence to re-initiate (Con∆) as potential mediators of the treatment effect, using logistic regression. Results: Logistic regression analysis including all potential mediators as predictors of initiation indicated the BMS∆ was the only statistically significant predictor (OR = 1.61, p = .010). When BMS∆ was removed Mot∆ (OR = 1.22 , p = .002) and PC∆ (OR = 1.67, p = .002) were statistically significant predictors of initiation. The MI-CBT intervention appeared to work primarily by increasing motivation to initiate DMT.