BACKGROUND Piriformis syndrome causes severe buttock and low back pain and numbness of the lower limbs, leading to difficulty in walking. The lack of unified diagnostic criteria for piriformis syndrome until 2018 made it difficult to diagnose; therefore, it is often underestimated, and some patients do not receive appropriate treatment. Treatment methods include local anesthetic injection, steroid injection, and local botulinum toxin injection. However, the most effective drug for the treatment of severe piriformis syndrome has not been established. This report aimed to propose a new and more effective treatment for piriformis syndrome with a minimal risk of adverse effects. CASE REPORT We performed ultrasound-guided hydro-dissection of the superficial and deep surfaces of the piriformis muscle under local anesthesia (a mixture of 18 mL of saline and 2 mL of 1% lidocaine) in 2 flexion, adduction, and internal rotation test-positive patients with tenderness of the piriformis muscle. In both patients, symptoms improved quickly after injection. One required hospital treatment but gradually returned to previous activities of daily living (ADL) status 5 days after admission and was then discharged. The other patient received 2 injections weekly to improve ADL status with continued lifestyle guidance. CONCLUSIONS Hydro-dissection by ultrasound-guided injection of a very low concentration of local anesthetic is effective and has lower risk of adverse effects, thus making it more convenient for the treatment of piriformis syndrome than conventional treatments, such as local anesthetics, steroids, and botulinum toxin injection.