Several nerve block procedures are available for post-thoracotomy pain management. In this randomized trial, the authors aimed to determine whether the analgesic effect of preoperative ultrasound-guided erector spinae plane block (ESPB) might be superior to that of intraoperative intercostal nerve block (ICNB) in pain control in patients undergoing minithoracotomy. University hospital. Sixty consecutive adult patients scheduled to undergo minithoracotomy for lung resection were enrolled. Patients were allocated randomly in a 1:1 ratio to receive either single-shot ESPB or ICNB. The primary outcome was the intensity of postoperative pain at rest, assessed with the numeric rating scale (NRS). The secondary outcomes were (1) dynamic NRS values (during cough); (2) perioperative analgesic requirements; (3) patient satisfaction, on the basis of a verbal scale (Likert scale); and (4) respiratory muscle strength, considering the maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) variation from baseline. The ESPB group showed lower postoperative static and dynamic NRS values than the ICNB group (p < 0.05). Total remifentanil consumption and requirements for additional analgesics were lower in the ESPB group (p < 0.05). Patient satisfaction was higher in the ESPB group (p < 0.001). A significant overall time effect was found in MIP and MEP variation (p < 0.001); ESPB values were higher at all points, reaching a statistically significant level at the first and sixth hours for MIP, and at the first, 12th, 24th, and 48th hours for MEP (p < 0.05). ESPB was demonstrated to provide superior analgesia, lower perioperative analgesic requirements, better patient satisfaction, and less respiratory muscle strength impairment than ICNB in patients undergoing minithoracotomy. Copyright © 2020 Elsevier Inc. All rights reserved.