Study objective To investigate the effective analgesia for video-assisted thoracic surgery. Design In this prospective non-inferiority study, we evaluated the postoperative analgesic effect of preoperative ultrasound-guided Erector Spinae Plane blocks (ESPB) on T4 and T6 levels in patients undergoing video-assisted thoracic surgery in comparison with paravertebral block (PVB) at the same intervertebral spaces. Setting A university hospital. Patients 66 patients scheduled to undergo video-assisted thoracic surgery under general anesthesia were included. Interventions Patients were randomly allocated to receive ultrasound-guided ESP blocks on T4 and T6 levels (Group ESPB, n = 33) or PVB (Group PVB, n = 33) with 30 mL 0.4% ropivacaine 30 min before anesthesia induction. A continuous flurbiprofen (8 mg/h) was infused postoperatively through a single-use infusion device and intravenous oxycodone supplied as analgesic rescue if needed, with bolus of oxycodone (1 mg) and lockout time being 10 min. Measurements The primary outcome was the postoperative oxycodone consumption at 48 h. Main results Intraoperative use of sufentanil and remifentanil were comparable between these two groups. Pain scores, oxycodone rescue and Quality of Recovery (QoR) 15 on postoperative day 1 and 2 were equivalent between these two groups. Postoperative oxycodone consumption was 7.9 ± 8.7 boluses in ESPB group and 6.9 ± 6.3 boluses in PVB group at 48 h. The cumulative 48 h difference i.e. Oxycodone boluseswith ESPB minus Oxycodone boluseswith PVB was 2 (95% CI -1, 5.6). The lower limit of the 95% CI for this difference was −1, which was within the predefined non-inferiority margin of −10 (Δ). Conclusions Ultrasound-guided ESPB applied before video assisted thoracic surgery was non-inferior in analgesic effect compared with PVB in terms of pain score, analgesic rescue consumption and quality of recovery. Brief summary statement Preoperative Erector spinae plane blocks (ESPB), when in combination with round-the-c...