BACKGROUND: This study was performed to investigate the efficacy and safety of intrathecal autologous bone marrowderived mesenchymal stem cells (MSCs) treatment for patients with ALS. METHODS: After a lead-in period for 3 months, 22 patients were treated with MSCs twice at an interval of 1 month. After initial MSCs injection, all patients were followed up for 3 months and their disease course, clinical characteristics were assessed. Disease status of patients were analyzed with ALS functional rating scale-revised (ALSFRS-R) for primary outcome measure, and additional clinical findings after treatment were all collected for secondary outcome measure and safety. Age and disease-duration matched patients with ALS were selected as a control group. RESULTS: During the follow-up period, MSCs treatment yielded a significant lesser change of ALSFRS-R score, compared to control group (1.54 vs 3.56, p<0.01). Moreover, the slop of decline of ALSFRS-R was significantly lower during the follow-up period, compared to the lead-in period in MSCs treatment group (2.68 vs 1.54, p=0.04), whereas the slopes during the two periods were not different in the control group (3.15 vs 3.56, p=0.37). MSCs treatment was well tolerated except for occurrences of transient headache, low back pain, and myalgia. CONCLUSIONS: Our results show that intrathecal MSCs injection can slow disease progression and might be used as a disease modifying modality as an alternative treatment choice in patients with ALS.