Abstract Background One of the main objectives of anesthesia is to alleviate the patient’s pain and agony, by ensuring the performance of surgical procedures without any discomfort. Elimination of postoperative pain is indispensable due to the central, peripheral and immunological stress response to tissue injury. So there is a need for extended analgesia without any side effects to achieve this goal. Objective To assess the analgesic efficiency and safety of both Modified Pectoral Nerve Block versus Serratus Block in cases of modified radical mastectomy (MRM). The duration of analgesia and effect on hemodynamic parameters were evaluated. Moreover, undesirable side effects were studied. Patients and Methods The purpose of this study was to evaluate the effect of both PECS II block versus and Serratus anterior block in patients undergoing modified radical mastectomy surgery. The duration of analgesia and effect on hemodynamics parameters were evaluated. Moreover, undesirable side effects were studied. forty patients were randomly allocated into two equal groups (20 patients): group (A) and group (B). Group (A): received a PECSII block with 30 mL of bupivacaine 0.25%. Group(B): received a serratus anterior plane block (SAPB) using the same volume of 30 ml bupivacaine 0.25%. Results This study demonstrated that PECSII and serratus blocks have comparable analgesic properties in patients undergoing modified radical mastectomy. Both blocks were associated with reduced postoperative pain intensity and morphine consumption, intraoperative fentanyl requirement, and prolonged analgesia. The two blocks were associated with hemodynamic stability and absence of major complications characterizes both blocks. Conclusion This study confirms that PECSII and serratus blocks provide similarly adequate analgesia following modified radical mastectomy.