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Despite increased public interest and research on intensive high-dose mental health interventions, much remains unknown about the mental health effects and safety of multi-day intensive high-dose mindfulness meditation training. Accordingly, we conducted a preregistered prospective intervention study among 89 adults who registered for 6-day insight mindfulness meditation retreats and 46 matched controls (M_age(SD_age) = 33.75 (9.50), 56.3% female). Retreat participants demonstrated significant improvements in well-being, negative affect, perseverative thinking, brooding rumination, and depression symptoms at 2-week follow-up compared to matched controls (η² range = .04-.08, ps < .05). Effects on positive affect, emotion regulation, and anxiety symptoms were not significant. The percentage of participants exhibiting statistically reliable deterioration in mental health at 2-week follow-up was equal or lower among retreat participants than matched controls, both in the full sample and in a subsample with clinically elevated depression and/or anxiety (ORs < 1). Findings suggest that a 6-day mindfulness meditation retreat can produce rapid improvements in mental health, comparable to effect sizes of much longer 8-week mindfulness-based programs. Findings also challenge concerns about adverse effects of intensive high-dose meditation retreats and suggest they may be a safe and effective intervention modality, even for clinically vulnerable adults struggling with depression or anxiety.Trial Registration: ClinicalTrials.gov registration ID NCT04749264.