OBJECTIVE: To evaluate the clinical safety and efficacy of botulinum toxin type B (MYOBLOC) in reducing myofascial pain associated with piriformis syndrome. DESIGN: This was a single-center, outpatient, open-label study of patients with piriformis syndrome. Subjects were treated unilaterally or bilaterally, depending on their symptoms. Evaluations and procedures were performed by a single examiner who was not blinded, and there were no control subjects in this case series. Each piriformis muscle was infiltrated from one injection site under electromyographic guidance with 5000 units of botulinum toxin type B. RESULTS: A total of 20 patients were enrolled in this study. Significant reductions in mean visual analog scale scores for buttock and hip pain were noted at weeks 4, 12, and 16 and for low back pain at weeks 2, 12, and 16. Visual analog scale scores for general and low back pain, pain radiating into lower limbs, and tingling were significantly lower at week 2 after injection, suggesting early onset. A total of 95% of patients reported fair to excellent improvement in pain. Botulinum toxin type B was considered to have fair to excellent efficacy in 90% of patients, as evaluated by the investigator rating of overall efficacy. Botulinum toxin treatment was well tolerated. Dry mouth was the most common treatment emergent adverse event, reported in 6 of 20 patients. CONCLUSIONS: Findings suggest the possibility that botulinum toxin type B may be of potential benefit in the treatment of pain attributed to piriformis syndrome.