Background: Studies on the effectiveness of multimodal analgesia, particularly in patients at higher perioperative risk from obstructive sleep apnoea (OSA), are lacking. We aimed to assess the impact of multimodal analgesia on opioid use and complications in this high-risk cohort. Methods: We conducted a population-based retrospective cohort study of OSA patients undergoing elective lower extremity joint arthroplasty (2006e16, Premier Healthcare database). Multimodal analgesia was defined as opioid use with the addition of one, two, or more non-opioid analgesic modes including, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, paracetamol/acetaminophen, peripheral nerve blocks, steroids, gabapentin/pregabalin, or ketamine. Multilevel multivariable regression models measured associations between multimodal analgesia and opioid prescription (primary outcome; oral morphine equivalents). Secondary outcomes included opioid-and OSA-related complications, and resource utilisation. Odds ratios (OR) or % change and 95% confidence intervals (CI) are reported. Results: Among 181 182 OSA patients included, 88.5% (n ¼ 160 299) received multimodal analgesia with increasing utilisation trends. Multivariable models showed stepwise beneficial postoperative outcome effects with increasing additional analgesic modes compared with opioid-only analgesia. In patients who received more than two additional analgesia modes (n ¼ 64 174), opioid dose prescription decreased by 14.9% (CI À17.0%; À12.7%), while odds were significantly decreased for gastrointestinal complications (OR 0.65, CI 0.53; 0.78), mechanical ventilation (OR 0.23, CI 0.16; 0.32), and critical care admission (OR 0.60, CI 0.48; 0.75), all P<0.0001.