We randomly allocated 50 women scheduled for radical mastectomy to pectoral nerves-2 (PECS-2) block (n = 25) or no block (n = 25), 20 and 22 of whom we analysed for the primary outcome of a cumulative 24-h postoperative morphine dose. We gave intra-operative sufentanil, magnesium, dexamethasone and droperidol. Participants received regular postoperative paracetamol, ibuprofen and patient-controlled intravenous morphine. Pectoral nerves-2 block reduced mean (SD) cumulative 24 h postoperative morphine dose from 9.7 (8.9) mg to 5.0 (5.4) mg and 48 h morphine dose from 12.8 (12.5) mg to 6.0 (6.5) mg, p = 0.04 for both. The mean (SD) pain scores 24 h and 48 h after surgery were similar with or without block: 0.8 (1.4) vs. 1.2 (1.9), p = 0.39; and 0.2 (0.4) vs. 0.9 (1.8), p = 0.09, respectively. Rates of postoperative nausea, vomiting and pruritus were unaffected. Rates of chronic pain at six postoperative months were 2/19 and 2/18 after block and no block, respectively, p = 0.95.