Question: In patients undergoing hip or knee arthroplasty, what is the effectiveness of intravenous (IV) versus oral acetaminophen as part of a standard perioperative pain regimen? Design: Randomized (unclear allocation concealment), blinded (unclear), controlled trial with 24 hours of follow-up. Setting: A hospital in Columbus, Ohio. Patients: 120 patients who were undergoing hip or knee arthroplasty. Exclusion criteria included known hypersensitivity, hepatic impairment, or liver disease. 100% of patients completed follow-up. Intervention: Patients were allocated to IV (n = 63) or oral (n = 57) acetaminophen, 1 g preoperatively and then every 6 hours postoperatively for 24 hours as part of a standard pain regimen, which included preoperative celecoxib, Oxycontin, and anti-nausea medication; intraoperative dexamethasone, tranexamic acid, and injection of bupivacaine with epinephrine at the surgical site; and postoperative hydropmorphone, oxycodone, Oxycontin, dexamethasone, celecoxib, and anti-nausea medication. Main outcome measures: Total narcotic use (hydromorphone-equivalents) and pain (visual analog scale [VAS]) were assessed every 4 hours for 24 hours after surgery. A sample size of 102 patients was needed to detect a difference of 0.5 on the pain VAS (80% power, α = 0.05). Main results: The IV and oral acetaminophen groups did not differ with regard to average hydromorphone-equivalents at 24 hours (3.71 versus 3.49, p = 0.76) or at any of the 4-hour intervals. The IV and oral acetaminophen groups did not differ with regard to average VAS pain scores in the first 24 hours (3.01 versus 3.40, p = 0.06) or when assessed at 4, 8, 12, 16, 20, or 24 hours; however, the IV acetaminophen group had lower VAS pain scores during the first 4 hours after surgery (3.38 versus 4.40, p = 0.03). Conclusions: In patients undergoing hip or knee arthroplasty, intravenous acetaminophen added to a standard pain regimen did not differ from oral acetaminophen for pain in the first 24 hours after surgery, except for the first 4 hours; intravenous and oral acetaminophen did not differ for total narcotic use in the first 24 hours. Source of funding: Not stated. [ABSTRACT FROM AUTHOR]