Introduction: Thromboembolic complications contribute substantially to perioperative morbidity and mortality. Routine laboratory tests do not detect patients with acquired or congenital hypercoagulability who may be at increased risk of perioperative thromboembolism. Rotational thromboelastometry (ROTEM) is a digitized modification of conventional thromboelastography that is stable and technically easy to use. We designed a prospective observational study to evaluate whether preoperative ROTEM can identify patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. Methods: Preoperative ROTEM analysis using extrinsic rotational thromboelastometry (EXTEM), intrinsic rotational thromboelastometry (INTEM), and fibrinogen rotational thromboelastometry (FIBTEM) activators was performed on 313 patients undergoing major non-cardiac surgery. Patients' medical records were reviewed after discharge for results of standard coagulation studies - partial thromboplastin time (PTT), international normalized ratio (INR), platelet count - and evidence of thromboembolic complications during their hospital stay. A thromboembolic complication was defined as a new arterial or deep venous thrombosis, catheter thrombosis, or pulmonary embolism diagnosed by ultrasound or spiral chest computed tomography. Results: Ten patients developed postoperative thromboembolic complications, of whom 9 had received standard prophylaxis with subcutaneous enoxaparin or heparin. There was no indication of by PTT, INR, or platelet count. Preoperative EXTEM and INTEM activators that assess fibrin clot formation and platelet interaction indicated that these patients had significantly lower clot formation time (CFT) and significantly higher alpha angle (a) and maximum clot firmness (MCF), compared to patients without thromboembolic complications. There was no significant difference for any parameter using FIBTEM activator, which excludes platelet interaction. Receiver operating characteristic (ROC) curves were constructed for these variables. INTEM clot firmness at 10 min (A10) was the best predictor of thromboembolic complications, with an ROC area under the curve of 0.751. Conclusions: Our results indicate that preoperative ROTEM assays that include fibrin clot and platelet interaction may detect patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. Future studies need to evaluate the clinical utility and cost effectiveness of preoperative ROTEM and better define the association between ROTEM values and specific hypercoagulable conditions.