Objective: To evaluate the effects of the Pecs II block on postoperative pain in patients undergoing breast reduction surgery. Materials and Methods: This prospective, comparative, and observational study was conducted with 53 patients, with American Society of Anesthesiologists I-II, between the ages of 18 and 65, and undergoing bilateral breast reduction surgery. The patients were divided into two groups: Pecs II block with general anesthesia (Pecs group; n = 26) and local infiltration anesthesia with general anesthesia (control group; n = 27). The patients' demographic data, duration of surgery and anesthesia, hemodynamic parameters, perioperative analgesia requirements, postoperative visual analog scale ( VAS) scores (at zero, one, three, six, nine, and 12 hours postoperative), the number of patients who needed analgesia at least once, the length of the hospital stay, and block-related complications were recorded. Results: There was no statistical difference in terms of the duration of surgery and anesthesia and hemodynamic parameters. Intraoperative total fentanyl consumption (128.85 +/- 25.19 mcg in the Pecs group and 227.77 +/- 44.58 mcg in the control group; P < .001) and postoperative analgesic requirement were significantly lower in the Pecs group (P < .001). The number of patients who needed analgesia at least once in the Pecs group was four (15.3%). Postoperative VAS scores were significantly lower (P < .001) and the length of the hospital stay was significantly shorter in the Pecs group (P < .001). No block-related complications were observed. Conclusion: Pecs II block with general anesthesia may significantly contribute to reducing intraoperative and postoperative analgesia requirements and provide long-lasting and more effective postoperative pain in breast reduction surgery.