Background: Thoracic epidural analgesia (TEA) was considered as the gold standard for postoperative analgesia in thoracic surgeries, particularly in bilateral procedures. However, it isn't routinely used as it is associated with some haemodynamic side effects. Erector spinae plane (ESP) block is recognized as a promising postoperative analgesia technique. Aim of the study: The primary outcome was to compare post-mastectomy pain control in TEA and ESP block groups, and secondary outcomes were to compare post-operative hypotension, number of morphine boluses, and patient satisfaction. Patient and Methods: Sixty female patients scheduled for elective mastectomy were enrolled in this study. Patients were allocated into 2 groups, 30 patients each. Group (TE) patients underwent ultrasoundguided single-shot TEA, while group (ES) were handled with ultrasoundguided single-shot ESP block. Peri-operative details, Post-operative hypotension, visual analog scale (VAS) assessment of pain, number of postoperative morphine boluses, and patient satisfaction were recorded. Results: Time needed to give block was shorter in the group (ES) (p<0.001). Group (ES) patients reported significantly lower pain scores according to VAS (P<0.001). Hypotension was more recorded in group (TE) patients, with statistical significance at 0 point (p<0.001). Required post-operative morphine boluses were significantly lower in the group (ES), as 3.3% of patients received 3 boluses compared to 27% in the group (TE) (p=0.01). More patients were highly satisfied with group ES (60%) than group TE (30%) (p=0.037). Conclusion: Ultrasound-guided ESP block is a choice with a better outcome in patients undergoing elective mastectomy as regards the lower frequency of hypotension, better efficiency, and patient satisfaction.