INTRODUCTION: The purpose of preventive analgesia based on regional blocks with local anesthetics is to avoid sharp and hard-to-control pain in the anterior side of thorax and axilla secondary to radical mastectomy. OBJECTIVE: Our aim was to compare the analgesic effectiveness of direct trans-operational block applied to nerves vs conventional analgesia using analgesic-antipiretic and antiinflammatory (AINES) drugs. MATERIAL AND METHODS: We designed a 1-year case-control study at the Hospital de Oncología of the Instituto Mexicano del Seguro Social's (IMSS's) Centro Medico Nacional Siglo XXI (CMN-SXXI) in Mexico City. A total of 112 patients were mastectomized under general anesthesia: Thirty one patients received preventive analgesia (cases) by direct transoperational infiltration of brachial and intercostal nerves III-VI; bupivacaine 1 mg/kg and buprenorphine 0.005 mg/kg in 15 ml were distributed among appropriate nerves accompanied by a single dose of AINES in emersion stage; during anesthetic emersion, 81 patients received conventional analgesia (control), including endovenous AINES alone or combined, and buprenorphine 0.3 mg or nalbuphine 10 mg. Three evaluations employing analog visual scale were conducted: recovery (immediate post surgery); floor (mediate), and following day. RESULTS: We studied 110 women and two men. Demographic, laboratory, anesthetic, and surgical variables were similar in both groups (p = not significant [ns]). In no case was post-surgical pain reported. Among controls, slight pain was reported by 13 patients, moderate pain by 66, and severe pain was reported by two patients, whereas in patients returned to their rooms on the floor, slight pain was reported by 38, moderate by 42, and severe by one. Finally, on the following day all patients reported slight pain. Types of pain included 15 patients with somatic pain, 10 with neuropathic, and 56 patients with mixed pain (p <0.0001). CONCLUSIONS: Preventive analgesia by direct transoperational block on nerves turned out to be an effective alternative with low level of systemic morbidity, which must be considered to prevent moderate and severe pain syndromes that are difficult to control in thoracic oncological surgery.