Gemcitabine-induced thrombotic microangiopathy (GITMA) is a rare yet devastating complication in patients receiving gemcitabine, especially at cumulative doses above 20,000 mg/m2. We report the case of a 72-year-old woman with metastatic pancreatic adenocarcinoma who developed severe thrombotic microangiopathy (TMA) during gemcitabine and nab-paclitaxel therapy. Her initial presentation included thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. A kidney biopsy confirmed TMA and, given the high likelihood this was related to gemcitabine, therapy was discontinued and the patient was transitioned to folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX).