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Abstract Background Erector spinae plane block (ESPB) is a promising technique for effective analgesia. It is still uncertain if ESPB offers the same opioid-sparing effect as thoracic paravertebral block (PVB) in midline incision for upper abdominal surgery. Methods The study is a prospective, bi-center, randomized, controlled, non-inferior trial. One hundred fifty-eight patients scheduled for upper abdominal surgery will be randomly assigned to receive bilateral ESPB or PVB before surgery. The primary outcome will be the equivalent cumulative analgesia dosage of sufentanil during the surgery, which is defined as the total dosage of sufentanil from anesthesia induction to tracheal extubation. The main secondary outcomes include postoperative complications and the quality of recovery-15 score at 24 h, 48 h, and 30 days after surgery. Discussion This study will assess the opioid-sparing efficacy of ESPB and PVB, complications, and the quality of recovery of two blocks. Trial registration ChiCTR2300073030 ( https://www.chictr.org.cn/ ). Registered on 30 June 2023.