Rhomboid intercostal block (RIB) is a novel regional analgesia procedure which controls pain after surgery involving the chest wall. The current study aimed to compare the postoperative analgesia of two different volumes of bupivacaine for an ultrasound (US)-guided RIB in cases undergoing modified radical mastectomy (MRM). Methods: This study was a randomized controlled double-blinded study that comprised 82 cases and was scheduled for MRM under general anesthesia (GA), cases were randomly assigned into 2 equal groups; RIB with 25 ml of 0.375% isobaric bupivacaine in 41 patients (Group V 25) and rhomboid intercostal plane block with 40 ml of 0.375% isobaric bupivacaine in 41 patients (Group V 40). Results: There were no significant differences between the two groups as regards demographic data, ASA score, and duration of surgery and post-anesthesia care unit (PACU) stay. In terms of pain assessment, post-operative VAS at 2, 4, 8, 16, and 24h postoperative during rest and arm movement were comparable in both groups and the total 24 hours postoperative morphine requirements has no significant difference between 2 groups . Conclusion: Regarding MRM and from the results of the current study we concluded that US-guided RIB provides efficient post-operative analgesia. In addition, both volumes provide comparable post-operative analgesic effects with regard to postsurgical 24hr opioid consumption, analgesic requirement, hemodynamics, and pain score.