Résumé : Background: We investigated the effect of a peri-operative opioid-free approach on postoperative patient comfort in patients undergoing breast cancer surgery. Subjects and Methods: From September 2014 to July 2015, 66 female patients of the Belgian Oncology Institut Jules Bordet were recruited. They were randomized into two groups: the first group received anesthesia with opioids for their breast cancer surgery, and the second group received opioid-free anesthesia. Patient comfort was evaluated 24 hours postoperatively through the QoR-40 score, with a difference of 15 points considered as being clinically relevant. Postoperative analgesia was provided through a piritramide patient-controlled analgesia device, during the first 24 hours. The hypothesis of this study was that opioid-free anesthesia would improve quality of recovery after anesthesia. Results: A statistically significant difference in postoperative QoR-40 score was observed between groups [Mean (SD) QoR-40 of 182.1/200 (13.9) in the opioid-free group, and 175.6/200 (14.80) in the opioid group; P = 0.04]. The clinical relevance of this finding is questionable, insofar as the difference of 15 points was not met. A statistically significant difference in postoperative piritramide usage was observed (8.1 (6.6) in the opioid-free group, and 13.1 (9.4) in the opioid group; P = 0.03). Conclusions: This randomized controlled trial shows, for the first time, equal comfort during the immediate postoperative period in patients having received opioid-free and conventional anesthesia for their breast cancer surgery. Opioid-free anesthesia in this indication appears safe, and may be associated with slightly reduced pain during the first 24 postoperative hours.