The efficacy of preemptive analgesia on postoperative pain is discussed. From experimental neurophysiological data, the present policy of preventive analgesia aims at precluding modifications of the nervous system secondary to a nervous lesion and the appearance of chronic pain, particularly of the neurogenic kind. The post-mastectomy pain syndrome (PMPS) falls within the realm of neurogenic pain and is still poorly understood and underestimated. This study evaluated the preemptive effect of a perioperative administration of an oral non steroid anti-inflammatory, the ibuprofen-arginine, on PMPS. Thirty patients scheduled for partial or total mastectomy with axillary dissection were prospectively and randomly assigned to 2 groups. The ibuprofen-arginine group (group I) (n = 15), received an oral administration of 400 mg of ibuprofen-arginine, 90 min before surgery, 2 h after surgery and then every 8 h in the first 32 postoperative hours. The control group (group C) received in doubled blind a placebo at the same time. At 6 months, we looked after pain or dysesthesia. We confirmed the diagnosis of PMPS in presence of association of diagnosis criterias. Fourteen patients in each group have been included. Eighty-six percent of the patients (13 patients in group I and 11 patients in group C) presented at 6 months dysesthesia of the upper member ipsilateral to the mastectomy and/or the operated breast, appearing either immediately or after a laps of time. Nine patients (group I) and 6 patients (group C) had PMPS. Postoperative radiotherapy and lymphoedema were statistically associated with PMPS (p = 0.019 and p = 0.011). The perioperative preventive administration of a non-steroid anti-inflammatory drug reduces neither the incidence of pain in the first post-operative months, nor the appearance of PMPS at 6 months. These results suggest that others factors than the nervous lesion may play a role in the occurrence of PMPS, as radiotherapy, lymphoedema, but also psychosocials factors.