BackgroundPain is frequent after cardiac surgery and source of multiple complications that can impair postoperative recovery. Regional anesthesia seems to be an interesting technique to reduce the pain in this context, but its effectiveness in improving recovery has been poorly studied so far. The objective of this study is to compare the effectiveness of two of the most studied chest wall blocks in cardiac surgery, i.e., the superficial and the deep parasternal intercostal plane blocks (SPIP and DPIP respectively), in addition to standard care, versus the standard care without regional anesthesia, on the quality of postoperative recovery (QoR) after cardiac surgery with sternotomy.MethodsThis is a single-center, single-blind, controlled, randomized trial with a 1:1:1 ratio. Patients (n= 254) undergoing cardiac surgery with sternotomy will be randomized into three groups: a control group with standard care and no regional anesthesia, a SPIP group with standard care and a SPIP, and a DPIP with standard care and a DPIP. All groups will receive the usual analgesic protocol. The primary endpoint is the value of the QoR evaluated by the QoR-15 at 24 h after the surgery.DiscussionThis study will be the first powered trial to compare the SPIP and the DPIP on global postoperative recovery after cardiac surgery with sternotomy.Trial registrationClinicalTrials.gov NCT05345639. Registered on April 26, 2022.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-023-07446-2.