Background The primary goal of modified radical mastectomy is to remove cancerous cells and reduce the risk of breast cancer spreading. This operation is associated with considerable acute postoperative pain and restricted shoulder movement. If this acute pain is neglected most patients will develop chronic post-mastectomy pain, which reduces the quality of life. Regional anesthesia using ultrasound-guided paravertebral nerve block or pectoral nerve block has become an ideal addition to general anesthesia for providing analgesia after breast cancer surgery. This was a randomized clinical trial conducted between February 2018 and February 2019. This study compared between the two nerve blocks regarding the efficacy in terms of analgesic consumption. Results The study included 30 female patients who were undergoing modified radical mastectomy under general anesthesia and randomly divided into 2 groups of 15 patients in each. This study showed there was a statistically significant increase in the amount of total fentanyl used intraoperatively in TPVB group than PECs group with p value = 0.008. Less VAS score in PECS group with statistically significant difference between groups at 4 h, 5 h, 6 h, and 8 h. More time needed for 1st requested rescue analgesia in PECS group with P value = 0.013. Patients in PECS group received a less total dose of fentanyl in the first 24 h postoperative with P value = 0.040. There was no statistically significant difference found between groups regarding postoperative complications. Conclusions In female patients undergoing breast surgeries, the PECs block can be used efficiently and safely, providing better pain relief than the TPVB and reducing intraoperative and postoperative opioids use.