Objective To evaluate the analgesic application of thoracic paravertebral blockade (TPVB) and transverse abdominal plane block (TAPB) for multiple costal margins after open liver surgery. Methods A total of sixty patients [American Society Anesthesiologists (ASA) Ⅰ‒Ⅲ］ who were scheduled for open liver surgery (with a classical reverse L‑shaped incision) were enrolled. The patients were divided into two groups according to the random number table method (n=30): a TPAB group (group TP) and a group of TAPB for multiple costal margins (group TA). Both groups received ultrasound guided nerve block before surgery. Group TP underwent bilateral TPVB at T7‒T8 and T8‒T9, while group TA underwent TAPB under bilateral costal margins and the classical site between the costal margin and the anterior inferior iliac spine, with a total of four block points. Then, both groups were compared and recorded for the duration of block procedures; the mean arterial pressure (MAP) and heart rate before incision (T0), after incision (T1), and at the times of block of the superior vena cava (T2), liver removal (T3) and stitching (T4); surgical duration, the inflow of liquid during surgery, the consumption of remifentanil, and the length of post‑anesthesia care unit (PACU) stay after surgery; the Visual Analogue Scale (VAS) scores at resting and during movement immediately after surgery (when patients were awaken after extubation and able to communicate normally), and 2 h and 6 h after surgery; and the number of patients requiring opioids within 6 h after surgery and the time when opioids were first given after surgery. Results Group TA presented shorter duration of block procedures than group TP (P<0.05). There was no statistical difference between the two groups as to MAP and heart rate at T0. However, compared with group TA, decreases in MAP and heart rate were found in group TP at T1, T2, T3 and T4 (P<0.05). Compared with group TA, group TP also presented remarkable decreases in the consumption of remifentanil during surgery, the length of PACU stay after surgery, and the VAS scores at resting and during movement immediately after surgery and 2 h after surgery (P<0.05). However, group TP required longer time when opioids were first given after surgery than group TA (P<0.05). There was no statistical difference in other indictors between the two groups (P>0.05). Conclusions During open liver surgery, compared with TAPB for multiple costal margins, TPVB can maintain more stable hemodynamics, require less doses of opioids and improve perioperative analgesia.