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This paper outlines the detailed statistical analysis plan for the primary data. The PERISAFE trial is a randomized, placebo\u2010controlled, blinded multicentre trial allocating 2904 hip\u2010 or knee\u2010arthroplasty patients 1:1 to ibuprofen 400\u2009mg \u00d73\/day or identical placebo \u00d73\/day for 8\u2009days postoperatively. The primary outcome is a composite of death, acute myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis, renal failure, major bleeding, re\u2010operation, gastrointestinal ulcer, or readmission within 90\u2009days postoperatively. Secondary outcomes are hospital\u2010free days within 90\u2009days postoperatively, a composite of ibuprofen and opioid\u2010related adverse reactions based on an 8\u2010day postoperative diary, and health\u2010related quality of life after 90\u2009days postoperatively. All randomized patients who undergo surgery will be included in all analyzes. Binary data will be analyzed using a mixed\u2010effects generalized linear model, count data will be analyzed using the van Elteren test, and continuous data will be analyzed using a mixed\u2010effects linear regression. Additionally, the win ratio will be calculated for the primary outcome. The statistical analyzes will be conducted in accordance with this pre\u2010planned statistical analysis plan with one interim analysis after the inclusion of 1400 patients. All analyzes will be adjusted for site. We expect that the PERISAFE trial will provide high\u2010quality data based on predefined detailed methodology regarding the safety of postoperative treatment with ibuprofen after elective hip and knee arthroplasties.<\/jats:p>","DOI":"10.1111\/aas.70062","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T11:58:53Z","timestamp":1748433533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Adverse Effects Associated With Ibuprofen Use After Major Orthopaedic Surgeries\u2014A Detailed Statistical Analysis Plan for the <scp>PERISAFE<\/scp> Randomized Clinical Trial"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-0920","authenticated-orcid":false,"given":"Christina C. 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