ABSTRACT Background Insufficient management of postoperative pain is a notable issue encountered by individuals after open-heart operations. The study aimed to evaluate the effect of ultrasound-guided pecto-intercostal fascial block (PIFB) and transversus thoracis muscle plane (TTB) on the analgesic efficacy in adult patients undergoing open-heart operations and the duration of mechanical ventilation (MV). Methods A randomized double-blind controlled trial was conducted on a cohort of 90 adult patients with elective open-heart surgery, namely valve replacement, with midline sternotomy. Patients were divided into three groups of similar size. The first group (control group) received conventional systemic analgesia alone, while the second group received bilateral TTB and the third group received bilateral PIFB, using ultra-sound guided technique. Results A significant reduction in NRS (Numeric Rating Scale) values was observed in both the TTB group and the PIFB group as compared to the control group at zero, three and 6-hour postoperative. The PIFB and TTB group exhibited an important delay in the initiation of first rescue analgesia, as well as a reduction in the overall intake of fentanyl for rescue purposes during a twenty-four-hour period. Additionally, the TTB group and the PIFB group demonstrated considerably shorter durations of mechanical ventilation as compared to the control group. Conclusions The utilization of ultrasound TTB and PIFB demonstrated efficacy in providing postoperative analgesia compared to the control group. This was evidenced by the less requirement for additional analgesic medication, reducing postoperative pain scores and a shorter duration of mechanical ventilation.