Abstract Background Breast cancer is the most common cancer in women in both the developed and less developed world. In 2012, it represented about 12 percent of all new cancer cases and 25 percent of all cancers in women. A procedure called Modified radical mastectomy is now a standard surgical treatment for early stage breast cancers. These procedures cause significant acute pain and may progress to chronic pain states in 25–60% of cases. Objective to evaluate the effectiveness of ultrasound guided Modefied pectoral nerve block (PEC II) versus Serratus Anterior plane block (SAPB) as a postoperative Analgesia in MRM. Regarding the time of the first analgesic dose and the total amount of analgesia consumed during the first 24 hrs inaddition to the pain score and incidence of complications. Patients and Methods After obtaining approval from the medical ethical committee in Ain Shams University, this study was conducted in Ain Shams University Hospitals. It included 70 female patients undergoing MRM were divided randomly into two groups, each group consisted of 35 patients; Group I patients received Modified PECS, Group II patients received Serratus Anterior Plane Block (SAPB). The two groups were compared regarding analgesic outcome by using the numeric rating score system, time for first for analgesic need and total consumption of opioid in the 1st 24 postoperative hours. Demographic data and post-operative hemodynamics were also assessed. Results The results of our study showed that there was no statistically significant difference between groups regarding demographic data. Also, there was a statistically significant decrease in Mean blood pressure (mmHg) in Group II compared with Group I from 1 hr. to 6 hrs postoperative. However, a statistically significant decrease in group II compared to group I regarding postoperative heart rate (beat/min) from 1 hr. to 6 hrs. Conclusion SAPB block was more effective in reducing postoperative pain scores for 1-6 hours and lower total 24-h postoperative opioid and analgesic consumption after MRM under general anesthesia, compared to Modefied PECS block.