Background: Anesthesiologists are always looking for the regional analgesic technique which is easy, safe, low complication rate and provides satisfactory analgesia. A retrolaminar block is a recent modified paravertebral technique for analgesia of thoracoabdominal procedures with a local anesthetic injected at the retrolaminar site. It has the advantage of being safe and easy compared to the traditional thoracic epidural analgesia (TEA) but is still under investigation. Objective: This study aims to compare the ultrasound guided bilateral retrolaminar block versus ultrasound guided thoracic epidural analgesia on pain relief after laparoscopic cholecystectomy. Study Design: A prospective randomized double-blinded clinical study. Setting:Academic University Hospitals. Methods: 52 adult patients were randomly allocated into two equal groups at the end of the surgery: Group (R) (n=26): received bilateral ultrasound guided retrolaminar block with 20 ml of bupivacaine 0.25% and 5ug/ml adrenaline (1:200000) in each side.and Group (T) (n=26): received ultrasound guided thoracic epidural analgesia with 20 ml of bupivacaine 0.25% and 5ug/ml adrenaline (1:200000). Results: The Numerical Rating Scale (NRS) scores both at rest and during cough were statistically significant lower in R group compared to T group at 30 min and 1 hour postoperatively. The pain scores were statistically significant lower for about 4 hours in R group compared to 6 hours in T group. The time for the first call of nalbuphine was highly statistically significant shorter in R group (233.04±5.27 min) compared to T group (353.77±5.16 min)[Mean difference -120.37,CI 95% (-123.6, -117.8)] p <0.001. The total amount of nalbuphine consumption in the first 12hrs was statistically significant decreased in T group (17.31±5.52 mg) compared to (27.69±5.52 mg) in R group [Mean difference 10.4,CI 95%(7.3-13.5)] p <0.001.The total number of patients who developed nausea and vomiting were statistically significant more in T group (9 patients) compared to R group (3 patients) p= 0.04. Moreover, hypotension was statistically significant more common among patients in T group (10 patients) compared to R group (3 patients) P=0.025. Both groups were comparable regarding to patient satisfaction. Limitations:Limited literature in the field of the present study and sensory dermatome assessment but it does not affect the results as we used ultrasound-guided technique. Conclusions:Single shot retrolaminar block provides adequate postoperative pain relief for about 4 hours compared to single shot thoracic epidural of about 6 hours. Satisfaction with both techniques was the same; about 2/3rds of patients were satisfied or very satisfied with either block. Institutional Review Board (IRB #6777-31-3-2021) Clinical trial ID:NCT04835415.