Background: Breast Surgery is becoming more and more common. Patients are often middle-aged women and with high public awareness around issues of breast cancer. The numbers are increasing. Breast surgery is an exceedingly common procedure and associated with an increased incidence of acute and chronic pain. Regional anesthesia techniques may improve postoperative analgesia for patients undergoing breast surgery. Objective: To assess the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) compared with thoracic epidural analgesia (TEA) for breast surgery. Patients and methods: This is a prospective randomized clinical study done at Aswan University Hospitals. The present study was conducted on sixty female patients ASA I-II, their ages ranged from 20-50 years and scheduled for unilateral breast surgery. The patients were allocated randomly into three groups (n=20 each) according to type of regional anesthesia administrated. Results: There was no significant difference between the studied groups in age, body weight, height and BMI. VAS pain scores throughout the first 24 hrs postoperative showed that there was highly statistically significant decrease in VAS in immediate till 6 hrs postoperative in SAPB group (VAS in group C was less than in groups A and B, P-value < 0.001). As regard to side effects, no complications in the studied groups were recorded such as pneumothorax, vascular puncture, or local anesthetic toxicity. Conclusion: Serratusanterior plane blockmaintained hemodynamic stability as compared to TE and it produced low pain scores and less total morphine consumption in the early postoperative period after unilateral breast cancer surgery. These advantages, suggest the usefulness of SAPB especially in outpatient surgery.