Background: Thoracic paravertebral block (TPVB) produces ipsilateral somatic and sympathetic nerve blockade in multiple contiguous dermatomes both above and below the site of injection.  The Aim of This Study: was to compare the effectiveness of ultrasound-guided TPVB versus intravenous (IV) sedative analgesic using midazolam / fentanyl in patients undergoing extracorporeal shock wave lithotripsy (ESWL) procedure. Patients and Methods: This prospective, randomized study was carried out on sixty patients aged 20-60 years, with radio-opaque renal stone not more than1.5cm. TPVB group (30 patients) received ipsilateral ultrasound-guided TPVB at the level T9-T10 using bupivacaine 0.25% (20 mL) about 30 minutes before the ESWL. Midazolam/fentanyl group (30 patients) received sedatives analgesic drugs using IV midazolam (0.05 mg / kg) and fentanyl (1 µg/kg) about 5 min before the ESWL. The VAS score during and 30 min post procedure, total dose of rescue analgesic consumption during ESWL procedure, the success rate of ESWL, the time needed to stone clearance, patient and operator satisfaction scores were recorded. Result: During and after ESWL procedure, the VAS scores were significantly higher in midazolam/fentanyl group than TPVB group (P < 0.05). The number of patients required rescue analgesic during ESWL was significantly higher in midazolam/fentanyl group compared to TPVB group (P < 0.05).The success rate of ESWL was insignificantly different between both groups (P > 0.05). The time needed to stone clearance was significantly shorter in TPVB group compared to midazolam/fentanyl group (P < 0.05). Conclusions: Ultrasound-guided TPVB provided more effective analgesia with reduced number of ESWL sessions and shorter time to renal stone clearance than IV midazolam/fentanyl.