BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is effective for relapse prevention in major depressive disorder (MDD). It reduces cognitive reactivity (CR) and rumination, and enhances self-compassion and mindfulness. Although rumination and mindfulness after MBCT are associated with relapse, the association of CR, rumination, self-compassion, and mindfulness with relapse before initiation of MBCT has never been investigated. METHODS: Data were drawn from two randomized controlled trials, including a total of 282 remitted MDD participants (≥3 depressive episodes) who had been using maintenance antidepressant medication (mADM) for at least 6 months before baseline. All participants were offered MBCT while either their mADM was maintained or discontinued after MBCT. CR, rumination, self-compassion, and mindfulness were assessed at baseline by self-rated questionnaires and were used in Cox proportional hazards regression models to investigate their association with relapse. RESULTS: CR and mindfulness were associated with relapse, independent of residual symptoms, previous depressive episodes, and mADM-use. Higher CR and lower mindfulness increased the risk of relapse. Self-compassion was not associated with relapse. For rumination, a significant interaction with mADM-use was found. Rumination was associated with relapse in patients who discontinued their mADM, while this effect was absent if patients continued mADM. CONCLUSIONS: These results show that CR, rumination, and mindfulness are associated with relapse in remitted MDD-patients before initiation of MBCT, independent of residual symptoms and previous depressive episodes. This information could improve decisions in treatment planning in remitted individuals with a history of depression.