Background: Anteromedial chest wall fascial plane blocks may serve as a valuable addition to postoperative multimodal pain management following median sternotomy for cardiothoracic surgeries. Objectives: This study aimed to evaluate the impact of implementing the pecto-intercostal fascial plane block (PIFB) in patients scheduled for off-pump coronary artery bypass (OPCAB) surgery. Methods: This randomized controlled study involved 40 adult patients aged 30 to 70 years undergoing OPCAB surgery. They were randomly assigned to two equal groups: Group PI received bilateral ultrasound (US)-guided PIFB with 20 mL of bupivacaine 0.25% with adrenaline 2.5 µg/mL, while group C (control group) received bilateral sham blocks with 20 mL of saline 0.9%. Pain scores in the postoperative period (primary outcome), perioperative analgesic consumption, time until extubation, and discharge from the intensive care unit (ICU) were assessed for both groups. Results: Postoperative pain scores, both at rest and during coughing, were significantly lower in group PI compared to group C. Group PI required significantly less fentanyl perioperatively and less tramadol for postoperative rescue compared to group C. The duration of postoperative ventilation and time to ICU discharge were significantly shorter in group PI than in group C. Conclusions: In patients undergoing OPCAB surgery, pre-incisional ultrasound-guided PIFB can be a beneficial and safe component of multimodal pain management. It provides improved postoperative pain control, reduces the need for perioperative opioids, and leads to faster extubation and ICU discharge.