OBJECTIVE: This study was undertaken to test the hypothesis that intramuscular botulinum toxin type A decreases chronic pain attributed to piriformis muscle syndrome to a greater extent than a similar injection with vehicle (saline) alone. DESIGN: This double-blind, single group, crossover study was performed at an outpatient university clinic. Nine women with chronic buttock, hip, and lower limb pain without evidence of lumbar disk herniation or nerve root impingement on imaging studies participated in the study. The analgesic efficacy of a fluoroscopic/electromyographically guided unilateral intramuscular piriformis injection with 100 units botulinum toxin type A was compared with a similar injection of vehicle alone. Visual analog pain scales (VASs) were used to measure pain intensity, distress, spasm, and interference with activities. RESULTS: No differences in mean VASs were detected between groups at baseline or after injection with vehicle. However, decreases were observed between baseline and post-botulinum toxin type A injection mean VASs, but only in one of four categories (interference with activities). VASs from every time point (days) were also compared with the average baseline VASs. After injection with vehicle, decreases were detected, but only in one of the four categories (distress). In comparison, after injection with botulinum toxin type A, decreases were observed under all VAS categories. CONCLUSIONS: VAS data suggest that intramuscular piriformis injection with 100 units of botulinum toxin type A can reduce pain to a greater extent than similar injections with vehicle alone.