BACKGROUND It remains unclear whether the opioid-sparing effects of dexmedetomidine seen in patients undergoing general anesthesia are reproducible in patients undergoing spinal anesthesia. We hypothesized that the administration of intravenous dexmedetomidine for sedation during total knee arthroplasty under spinal anesthesia would decrease postoperative morphine consumption in the first 24 hr following surgery. METHODS We conducted this prospective double-blind randomized-controlled trial in 40 patients (American Society of Anesthesiologists physical status I-III) undergoing total knee arthroplasty with a standardized spinal anesthetic. Patients were randomized to receive either a dexmedetomidine loading dose of 0.5 µg·kg(-1) over ten minutes, followed by an infusion of 0.5 µg·kg·hr(-1) for the duration of the surgery, or a normal saline loading dose and an infusion of an equivalent volume. The primary outcome was the consumption of morphine delivered via patient-controlled analgesia in the first 24 hr following surgery. RESULTS The mean (SD) cumulative morphine at 24 hr in the dexmedetomidine group was 29.2 (11.2) mg compared with 61.2 (17.2) mg in the placebo group (mean difference, 32.0 mg; 95% confidence interval, 22.7 to 41.2; P < 0.001). In the dexmedetomidine group, there was a delay in the time to first analgesic request (P = 0.003) and a reduction in the mean morphine use at six and 12 hr following surgery (both P < 0.001). CONCLUSIONS Dexmedetomidine was associated with a significant decrease in morphine use in the first 24 hr following total knee arthroplasty. Our study shows that an intraoperative infusion of dexmedetomidine for sedation in patients receiving spinal anesthesia can produce postoperative analgesic effects. This offers another potential adjunct in the multimodal pain management of these patients. This trial was registered at ClinicalTrials.gov (identifier NCT02026141).