OBJECTIVE: Mindfulness is an established approach to reduce distress and stress reactivity by improving awareness and tolerability of thoughts and emotions. This study compares mindfulness training to sleep hygiene in persons with multiple sclerosis (PWMS) who report chronic insomnia, examining sleep efficiency (SE), self-reported sleep quality and quality of life. METHODS: Fifty-three PWMS were randomized (1:1) in a single-blinded, parallel group design to ten, two-hour weekly sessions of Mindfulness Based Stress Intervention for Insomnia (MBSI-I) over a span of ten weeks or a single, one hour sleep hygiene (SH) session over one day. The primary outcome measure was SE, measured by the Fitbit™ Charge 2 wrist device, at 10 and 16 weeks from the start of study interventions. Self-report outcomes included the Pittsburg Sleep Quality Rating Scale (PSQI), Insomnia Severity Index (ISI) and the Multiple Sclerosis Quality of Life Inventory (MSQLI). Nineteen participants in the MBSI-I group and 24 in the SH group completed the primary study. Subsequently, ten participants in the original SH group participated in the 10-week MSBI-I course and their data was added to the MBSI-I cohort (eMSBI-I). RESULTS: While neither SE nor the PSQI showed significant differences between MBSI-I, eMBSI-I and SH groups, ISI improved in both the MSBI-I and eMBSI-I vs SH at 10 weeks (p = 0.0014 and p = 0.0275) but not 16 weeks. However, pre and post assessments within the MBSI-I and eMBSI-I cohorts did show significant improvement in the PSQI and ISI at 10 and 16 weeks, while SH was significant in the ISI only at 16 weeks. Several quality of life measurements, including fatigue, mental health and cognitive function favored the mindfulness cohorts. CONCLUSION: This pilot study demonstrates beneficial effects of MBSR on insomnia, sleep quality and quality of life in PWMS. TRIAL REGISTRATION: NCT03949296. 14 May 2019.