Pectoral nerve blocks (PECNB) have been demonstrated to deliver adequate analgesia and reduce opioid dose following modified radical mastectomy (MRM). The pain associated with peripheral neuropathy and spinal cord injury and persistent phantom limb pain may be relieved by low-dose intravenous (IV) ketamine (KET). The purpose of this research is to evaluate the effectiveness as well as safety of ultrasound guided (US) modified PECNB with Bupivacaine (BVC) and KET in comparison to BVC alone in patients having MRM for pain relief. Methods: This prospective randomized single blinded clinical research was carried out in the National Cancer Institute (NCI) on adult females 20 to 60 years old, BMI of 25 – 40 kg/m2 and ASA scoring system: ASAI and ASAII suffering from breast cancer arranged for MRM. Cases were divided into two equal comparable groups: group I received US modified ECNB with BVC and group II received US- modified PECNB with BVC plus KET. Results: There was no statistically meaningful variation between the groups concerning intraoperative heart rate (HR), mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2). Visual analogue scale (VAS) was significantly less in group II versus I at 12h postoperatively (P value <0.001) and was insignificantly different at 0.5, 6, 18 and 24h postoperatively. Time of 1st rescue analgesia was significantly delayed at group II versus I (P value <0.001). Total morphine requirements were significantly less in group II versus I (P value <0.001). Incidence of postoperative nausea and vomiting (PONV) was 10 (12.05%) cases in group I and 2 (2.41%) cases in group II. PONV was significantly less in group II versus I (P value =0.002). Conclusions: Patient discomfort, total opioid dosage, and PONV were all decreased when Ketamine was added to US modified Pectoral nerve block with Bupivacaine for MRM.