Background: Thoracic epidural analgesia is considered the gold standard for pain relief in video-assisted thoracoscopic surgery. This neuraxial technique blocks pain sensation by injecting local anesthetic in the epidural space near the spinal cord to block spinal nerve roots. Recently, the erector spinae plane block has been introduced as a practical alternative to the thoracic epidural. This interfascial regional anesthesia technique interrupts pain sensation by injecting local anesthetic in between the muscular layers of the thoracic wall. Several case series and three RCTs described it as an effective pain management technique in video-assisted thoracoscopic surgery. (1–5)The objective of this study is to test the hypothesis that a continuous erector spinae plane block is non-inferior in terms of the quality of recovery as measured by the Quality of Recovery-15 score compared to continuous thoracic epidural analgesia in patients undergoing elective unilateral video-assisted thoracoscopic surgery.Methods: This is a prospective randomized open label non-inferiority trial. A total of 90 adult patients undergoing video-assisted thoracoscopic surgery will be randomized 1:1 to receive either pain treatment with continuous erector spinae plane block (study group) or continuous thoracic epidural analgesia (control group). The primary endpoint is the quality of recovery as measured by the Quality of Recovery-15 score. Secondary endpoints are postoperative pain as Numerical Rating Score scores, length of hospital stay, failure of analgesic technique, postoperative morphine-equivalent consumption, itching, nausea and vomiting, total operative time, complications related to surgery, perioperative hypotension, complications related to pain treatment, duration of bladder catheterization, time of first assisted mobilization >20 meters and of mobilization to sitting in a chair. Discussion: This randomized controlled trial aims to confirm whether a continuous erector spinae plane block can equal analgesic effect as regional anesthesia technique compared with a thoracic epidural in patients undergoing video-assisted thoracoscopic surgery.