Background: Breast cancer is among the most frequently diagnosed malignancies in women. A variety of surgical procedures are necessary to treat it, including lumpectomy and mastectomy. Aim and objectives: To compare the efficiency of ESP block and thoracic epidural block in perioperative pain control for breast surgery regarding the period of effective analgesia from the block until the first analgesic dose is required. Patients and Methods: This was a randomized, double-blinded comparative study performed on 80 female cases who were scheduled for conservative breast surgery in the operating room at Beni-Suef University Hospitals through the period from November 2020 to February 2023. Results: The pain score at 1 hour, 8, 12, & 24 hours was statistically significantly greater in the thoracic epidural block group (p < 0.001), while there wasn’t statistically significant variance among the two groups as regards VAS-4hr and the mean required dose of pethidine along the 24 hours (p = 0.075 & 0.376, respectively), and the mean length of effective analgesia was statistically significantly longer in the ESP Block group (p < 0.001). Conclusion: U/S-guided ESP block is a more beneficial choice with regard to outcomein cases being subjected to mastectomy than U/S-guided thoracic epidural analgesia in terms of less post-surgery opioid need, lower frequency of hypotension, and longer duration of effective analgesia.