Objective: To determine whether in post-mastectomy breast cancer patients, PEC II block plus single-dose intravenous analgesia is more effective than single-dose intravenous analgesia in treating postoperative pain. Methods: An cohort study was conducted between June and September 2022 with 60 breast cancer patients who underwent unilateral mastectomy. Two groups of 30 patients each were formed: one received PECS II Block plus EV Analgesia and the other only EV Analgesia. Inclusion criteria covered patients with ASA physical status 1 or 2, aged 18 to 70 years, and excluded those with drug allergies, serious diseases and those who refused to participate. Results: Patients who received EV Analgesia alone reported higher values of pain measured by the Visual Analog Scale compared to those who received PECS II Block plus EV Analgesia, with significant differences (p = 0.001). In terms of adverse effects, all patients in the PECS II Block and EV Analgesia group experienced no negative effects, while in the EV Analgesia only group, 100% required rescue analgesia, and there were reports of vomiting, headache and nausea. Conclusion: PECS II Block in combination with EV Analgesia proved to be more effective in postoperative pain control in patients undergoing unilateral mastectomy for breast cancer, significantly reducing the need for rescue analgesia and the occurrence of adverse effects compared to EV Analgesia alone.