Tizanidine, an imidazoline that acts as an agonist at alpha 2-adrenergic receptors, has been shown to be effective in reducing spasticity caused by MS. This multicenter study (14 sites) assessed the efficacy and safety of oral tizanidine in patients who had spinal cord injury of > 12 months' duration. Of the 124 patients admitted to the study, 78 completed it. Tizanidine was titrated to an optimized dosage in each patient to a maximum of 36 mg/d. Muscle tone, assessed by Ashworth score, was significantly reduced (p = 0.0001) by tizanidine treatment in comparison with placebo. Video motion analysis of the pendulum test showed improvement in the tizanidine-treated patients vs placebo (p = 0.04) and showed a significant correlation with the Ashworth score (p < 0.001). No significant alterations in muscle strength or vital signs were noted in either treatment group. The most common adverse events during tizanidine treatment were somnolence, xerostomia, and fatigue. It was concluded that, overall, tizanidine is effective in reducing spasticity in patients with spinal cord injury.