Background and objectives The significance of intravenous over oral acetaminophen (APAP) as part of multimodal analgesic protocols is contested, particularly when considering its relatively high price and use in a surgical cohort such as total hip or knee arthroplasty (THA/TKA), which generally tolerates oral medications. This study aims to elucidate APAP’s effectiveness in a large, population-based patient sample.

Methods 1 039 647 THA/TKA procedures were sampled from the Premier Healthcare claims database 2011–2016. APAP use was categorized by intravenous/oral and use on the day of surgery, postoperative day 1 and thereafter. Outcomes were opioid utilization (in oral morphine equivalents), length and cost of hospitalization, and opioid-related adverse effects (respiratory, gastrointestinal, and naloxone use as a proxy). Mixed-effects models measured the associations between intravenous/oral APAP use and outcomes. Percent (%) change and 95% CIs are reported.

Results Overall, 23.6% (n=245 454) of patients received intravenous APAP; of these, 56.3% (n=138 180) received just one dose on the day of surgery. After adjustment for relevant covariates, particularly use of >1 dose of intravenous APAP (compared with no use) on postoperative day 1 was associated with −6.0% (CI −7.2% to −4.7%) reduced opioid utilization; this was −10.7% (CI −11.4% to -9.9%) for use of > 1 dose oral APAP on postoperative day 1. Further comparisons regarding other outcomes also favored oral (over intravenous) APAP.

Conclusions These results do not support the routine use of intravenous APAP in patients undergoing lower joint arthroplasty, especially since oral APAP shows more beneficial outcome patterns.