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Piperacillin\u2013tazobactam (PTZ) has been associated with coagulation disruptions, potentially leading to severe bleeding when combined with anticoagulants like rivaroxaban. This report describes the first known case of massive gastrointestinal (GI) bleeding potentially associated with PTZ in a rivaroxaban\u2010treated patient, successfully managed by discontinuing both drugs. We present a 52\u2010year\u2010old male with deep vein thrombosis on rivaroxaban, admitted for severe left leg cellulitis. Shortly after starting PTZ, he experienced massive GI bleeding with hematochezia, hematemesis, and syncope, requiring urgent intervention, cessation of both medications, and esophagogastroduodenoscopy (EGD), which revealed minor erosions. The temporal relationship suggests a possible PTZ\u2010induced hemostasis disruption or interaction with rivaroxaban. This case highlights the need for research into PTZ\u2013anticoagulant interactions and emphasizes vigilant monitoring and timely management to reduce life\u2010threatening bleeding risks in anticoagulated patients.<\/jats:p>","DOI":"10.1155\/carm\/6053487","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T13:03:17Z","timestamp":1769864597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rivaroxaban and Piperacillin\u2013Tazobactam: Case of Massive Gastrointestinal Bleeding"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-769X","authenticated-orcid":false,"given":"Abbas","family":"Mohammadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoud","family":"Bitarafan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Korosh 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