Combined regional and general anesthesia are often used for the management of breast cancer surgery. Thoracic spinal block, thoracic epidural block, thoracic paravertebral block, and multiple intercostal nerve blocks are the regional anesthesia techniques which have been used in breast surgery, but some anesthesiologists are not comfortable because of the complication and side effects. In 2012, Blanco et al introduced pectoralis nerve (Pecs) II block or modified Pecs block as a novel approach to breast surgery. This study aims to determine the effectiveness of combined ultrasound-guided Pecs II block and general anesthesia for reducing intra- and postoperative pain from modified radical mastectomy. Fifty patients undergoing modified radical mastectomy with general anesthesia were divided into two groups randomly (n=25), to either Pecs (P) group or control (C) group. Ultrasound-guided Pecs II block was done with 0.25% bupivacaine (P group) or 0.9% NaCl (C group). Patient-controlled analgesia was used to control postoperative pain. Intraoperative opioid consumption, postoperative visual analog scale (VAS) score, and postoperative opioid consumption were measured. Intraoperative opioid consumption was significantly lower in P group (≤0.05). VAS score at 3, 6, 12, and 24 hrs postoperative were significantly lower in P group (≤0.05). Twenty-four hours postoperative opioid consumption was significantly lower in P group (≤0.05). There are no complications following Pecs block in both groups, including pneumothorax, vascular puncture, and hematoma. Combined ultrasound-guided Pecs II block and general anesthesia are effective in reducing pain both intra- and postoperatively in patients undergoing modified radical mastectomy. Ultrasound-guided Pecs II block is a relatively safe peripheral nerve block.