Background: Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain. Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries. Objectives: This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery.Study Methods: This study is registered after approval by the ethics committee benha university, Egypt. 120 patients aged 30 – 60 years scheduled for modified radical mastectomy were enrolled and randomly assigned into 4 groups (30 patients each): group I patients were given general anesthesia onlygroup II were given , Pecs block with 30 mL of 0.25% bupivacaine only. GroupIII were ginven , Pecs block with 30 mL of 0.25% bupivacaine and Ketamine 1mgkg. groupIV patients were given ultrasound-guided, Pecs block with insertion of 2 catheters for booster doses. Patients were followed up for 48 hours postoperatively for vital signs, VAS score, first request of rescue analgesia and total morphine consumption, sedation score, and side effects. Results: Ketamine plus bupivacaine in Pecs block compared to bupivacaine aloner and insertion of catethet prolonged the mean time of first request of analgesia (18.55 ± 1.97), (12.50 ± 2.61), respectively (P < 0.001), reduced total morphine consumption (12.51 ± 4.62), (18.85 ± 6.27), respectively (P = 0.016). With no significant difference in hemodynamics, respiratory rate, oxygen saturation, VAS and sedation scores, and side effects observed between the groups (P > 0.05). Conclusion: The addition of ketamine to modified Pecs block and insertion of catheter prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy.