Acute pain services have received widespread acceptance and formal support from institutions and organizations, but available evidence on their costs and benefits is scarce. Although there is good agreement on the provision of acute pain services after many major surgical procedures, there are other procedures for which the benefits are unclear. Data are required to justify any expansion of acute pain services. In this randomized, controlled clinical trial we compared the costs and effects of acute pain service care on clinical outcomes with conventional pain management on the ward. Patients included in the trial were considered by their anesthesiologist to have either arm be suitable for the procedure. Four hundred twenty-three patients undergoing major elective surgery were randomized either to an anesthesiologist-led, nurse-based acute pain service group with patient-controlled analgesia or to a control group with IM or IV boluses of opioid analgesia. Both groups were treated with medications to treat opioid-related adverse effects and received the usual care from health professionals assigned to the ward. The main outcome measures were quality of recovery scores, pain intensity measures, global measure of treatment effectiveness, and overall pain treatment cost. Cost-effectiveness acceptability curves were drawn to detect a difference in the joint cost-effect relationship between groups. There was no difference in quality of recovery score on postoperative day 1 between treatment and control groups (mean difference, 0; 95% confidence interval [CI], -0.7 to 0.7; P = 0.94) or in the rate of improvement in quality of recovery score (mean difference, -0.1; 95% CI, -0.4 to 0.1; P = 0.34). The proportion of patients with 1 or more days of highly effective pain management was higher in the acute pain service group than in the control group (86% vs. 75%; P < 0.01). Costs were higher in the acute pain service group (mean difference, US$46; 95% CI, $44 to $48 per patient; P < 0.001). A cost-effectiveness acceptability curve showed that the acute pain service was more cost effective than was control for providing highly effective pain management if the decision maker was willing to pay more than US$546 per patient per 1 day with highly effective treatment. In extending the role of the acute pain service to a specific group of major surgical procedures, the acute pain service was likely to be cost effective.