We conducted a randomized, double-blind trial to evaluate the early and late analgesic effect of preoperative wound infiltration with bupivacaine 0.25% (40 mL) compared to placebo (NaCl 0.9%, 40 mL) in patients undergoing major surgery. Forty-one patients scheduled for elective hysterectomy during general anesthesia were included. The pain management focused on pain prevention, including preoperative administration of nonsteroidal antiinflammatory drugs (NSAIDs), and peroperative administration of opioids. Postoperatively patients received buprenorphine and/or acetaminophen on demand. A significant difference between treatments was evident in the 3-day postoperative trial period. With identical pain scores in the two groups, the requested total amount of buprenorphine was greater in the placebo group (2.0 [0-5.1] mg) (median and [range]) than in the bupivacaine group (0.8 [0-2.8] mg) (P < 0.05). The demand for analgesics occurred earlier in those who received placebo (225 min) than in those who received bupivacaine (345 min), but did not reach the level of significance. In conclusion, preoperative wound infiltration with bupivacaine improved immediate and late postoperative pain management after hysterectomy compared to placebo.